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Open Access 01-12-2024 | Review

PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies

Authors: Menglei Jin, Jun Fang, Junwen Peng, Xintian Wang, Ping Xing, Kunpeng Jia, Jianming Hu, Danting Wang, Yuxin Ding, Xinyu Wang, Wenlu Li, Zhigang Chen

Published in: Molecular Cancer | Issue 1/2024

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Abstract

Immunotherapy targeting programmed cell death-1 (PD-1) and PD-L1 immune checkpoints has reshaped treatment paradigms across several cancers, including breast cancer. Combining PD-1/PD-L1 immune checkpoint blockade (ICB) with chemotherapy has shown promising efficacy in both early and metastatic triple-negative breast cancer, although only a subset of patients experiences durable responses. Identifying responders and optimizing immune drug selection are therefore critical. The effectiveness of PD-1/PD-L1 immunotherapy depends on both tumor-intrinsic factors and the extrinsic cell-cell interactions within the tumor microenvironment (TME). This review systematically summarizes the key findings from clinical trials of ICBs in breast cancer and examines the mechanisms underlying PD-L1 expression regulation. We also highlight recent advances in identifying potential biomarkers for PD-1/PD-L1 therapy and emerging evidence of TME alterations following treatment. Among these, the quantity, immunophenotype, and spatial distribution of tumor-infiltrating lymphocytes stand out as promising biomarkers. Additionally, we explore strategies to enhance the effectiveness of ICBs in breast cancer, aiming to support the development of personalized treatment approaches tailored to the unique characteristics of each patient’s tumor.
Literature
1.
2.
go back to reference Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L. Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol. 2019;20(3):e175–86.PubMedCrossRef Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L. Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol. 2019;20(3):e175–86.PubMedCrossRef
3.
go back to reference Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast Cancer. N Engl J Med. 2020;382(9):810–21.PubMedCrossRef Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast Cancer. N Engl J Med. 2020;382(9):810–21.PubMedCrossRef
4.
go back to reference Javier, Cortes, et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. JCO. 2020;38:1000–1000.CrossRef Javier, Cortes, et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. JCO. 2020;38:1000–1000.CrossRef
5.
go back to reference Schmid P, Cortes J, Dent R, et al. Event-free survival with Pembrolizumab in Early Triple-negative breast Cancer. N Engl J Med. 2022;386(6):556–67.PubMedCrossRef Schmid P, Cortes J, Dent R, et al. Event-free survival with Pembrolizumab in Early Triple-negative breast Cancer. N Engl J Med. 2022;386(6):556–67.PubMedCrossRef
7.
go back to reference Ramos P, Bentires-Alj M. Mechanism-based cancer therapy: resistance to therapy, therapy for resistance. Oncogene. 2015;34(28):3617–26.PubMedCrossRef Ramos P, Bentires-Alj M. Mechanism-based cancer therapy: resistance to therapy, therapy for resistance. Oncogene. 2015;34(28):3617–26.PubMedCrossRef
8.
go back to reference Nanda R, Chow LQ, Dees EC, et al. Pembrolizumab in patients with Advanced Triple-negative breast Cancer: phase ib KEYNOTE-012 study. J Clin Oncol. 2016;34(21):2460–7.PubMedPubMedCentralCrossRef Nanda R, Chow LQ, Dees EC, et al. Pembrolizumab in patients with Advanced Triple-negative breast Cancer: phase ib KEYNOTE-012 study. J Clin Oncol. 2016;34(21):2460–7.PubMedPubMedCentralCrossRef
9.
go back to reference Emens LA, Cruz C, Eder JP, et al. Long-term clinical outcomes and biomarker analyses of Atezolizumab Therapy for patients with metastatic triple-negative breast Cancer: a phase 1 study. JAMA Oncol. 2019;5(1):74–82.PubMedCrossRef Emens LA, Cruz C, Eder JP, et al. Long-term clinical outcomes and biomarker analyses of Atezolizumab Therapy for patients with metastatic triple-negative breast Cancer: a phase 1 study. JAMA Oncol. 2019;5(1):74–82.PubMedCrossRef
10.
go back to reference Winer EP, Lipatov O, Im SA, et al. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(4):499–511.PubMedCrossRef Winer EP, Lipatov O, Im SA, et al. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(4):499–511.PubMedCrossRef
11.
go back to reference Emens LA, Adams S, Barrios CH, et al. First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. Ann Oncol. 2021;32(10):1308.PubMedCrossRef Emens LA, Adams S, Barrios CH, et al. First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. Ann Oncol. 2021;32(10):1308.PubMedCrossRef
12.
go back to reference Schmid P, Rugo HS, Adams S, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(1):44–59.PubMedCrossRef Schmid P, Rugo HS, Adams S, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(1):44–59.PubMedCrossRef
13.
go back to reference Miles D, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32(8):994–1004.PubMedCrossRef Miles D, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32(8):994–1004.PubMedCrossRef
14.
go back to reference Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817–28.PubMedCrossRef Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817–28.PubMedCrossRef
15.
go back to reference Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: the randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med. 2021;27(2):250–5.PubMedCrossRef Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: the randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med. 2021;27(2):250–5.PubMedCrossRef
16.
go back to reference Domchek SM, Postel-Vinay S, Im SA, et al. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol. 2020;21(9):1155–64.PubMedCrossRef Domchek SM, Postel-Vinay S, Im SA, et al. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol. 2020;21(9):1155–64.PubMedCrossRef
17.
go back to reference Rugo HS, Kabos P, Beck JT, et al. Abemaciclib in combination with pembrolizumab for HR+, HER2- metastatic breast cancer: phase 1b study. NPJ Breast Cancer. 2022;8(1):118.PubMedPubMedCentralCrossRef Rugo HS, Kabos P, Beck JT, et al. Abemaciclib in combination with pembrolizumab for HR+, HER2- metastatic breast cancer: phase 1b study. NPJ Breast Cancer. 2022;8(1):118.PubMedPubMedCentralCrossRef
18.
go back to reference Loi S, Giobbie-Hurder A, Gombos A, et al. Pembrolizumab plus Trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Lancet Oncol. 2019;20(3):371–82.PubMedCrossRef Loi S, Giobbie-Hurder A, Gombos A, et al. Pembrolizumab plus Trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Lancet Oncol. 2019;20(3):371–82.PubMedCrossRef
19.
go back to reference Emens LA, Esteva FJ, Beresford M, et al. Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Lancet Oncol. 2020;21(10):1283–95.PubMedCrossRef Emens LA, Esteva FJ, Beresford M, et al. Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Lancet Oncol. 2020;21(10):1283–95.PubMedCrossRef
20.
go back to reference Gianni L, et al. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIP Michelangelo randomized study. Ann Oncol S. 2022;0923–7534:00113–2. Gianni L, et al. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIP Michelangelo randomized study. Ann Oncol S. 2022;0923–7534:00113–2.
21.
go back to reference Mittendorf EA, Zhang H, Barrios CH, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396(10257):1090–100.PubMedCrossRef Mittendorf EA, Zhang H, Barrios CH, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396(10257):1090–100.PubMedCrossRef
22.
go back to reference Loibl S, et al. Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC). JCO. 2021;39:506–506.CrossRef Loibl S, et al. Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC). JCO. 2021;39:506–506.CrossRef
23.
go back to reference Nanda R, Liu MC, Yau C, et al. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete response in women with early-stage breast Cancer: an analysis of the Ongoing phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol. 2020;6(5):676–84.PubMedCrossRef Nanda R, Liu MC, Yau C, et al. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete response in women with early-stage breast Cancer: an analysis of the Ongoing phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol. 2020;6(5):676–84.PubMedCrossRef
24.
go back to reference Dieci MV, Guarneri V, Tosi A, et al. Neoadjuvant Chemotherapy and Immunotherapy in Luminal B-like breast Cancer: results of the phase II GIADA trial. Clin Cancer Res. 2022;28(2):308–17.PubMedCrossRef Dieci MV, Guarneri V, Tosi A, et al. Neoadjuvant Chemotherapy and Immunotherapy in Luminal B-like breast Cancer: results of the phase II GIADA trial. Clin Cancer Res. 2022;28(2):308–17.PubMedCrossRef
25.
go back to reference Loi S, Curigliano G, Salgado R, Diaz RIR, Delaloge S, Garcia CIR et al. Biomarker results in high-risk estrogen receptor positive, Human Epidermal Growth Factor Receptor 2 negative primary breast Cancer following neoadjuvant chemotherapy ± nivolumab: an exploratory analysis of CheckMate 7FL. Cancer Res. 2024;84(9). Loi S, Curigliano G, Salgado R, Diaz RIR, Delaloge S, Garcia CIR et al. Biomarker results in high-risk estrogen receptor positive, Human Epidermal Growth Factor Receptor 2 negative primary breast Cancer following neoadjuvant chemotherapy ± nivolumab: an exploratory analysis of CheckMate 7FL. Cancer Res. 2024;84(9).
26.
go back to reference Cardoso F et al. KEYNOTE-756: phase 3 study of neoadjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo), followed by adjuvant pembro or pbo + endocrine therapy (ET) for early-stage high-risk ER+/HER2– breast cancer. ESMO Congress 2023, LBA21. Cardoso F et al. KEYNOTE-756: phase 3 study of neoadjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo), followed by adjuvant pembro or pbo + endocrine therapy (ET) for early-stage high-risk ER+/HER2– breast cancer. ESMO Congress 2023, LBA21.
27.
go back to reference McGranahan N, Furness AJ, Rosenthal R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463–9.PubMedPubMedCentralCrossRef McGranahan N, Furness AJ, Rosenthal R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463–9.PubMedPubMedCentralCrossRef
28.
go back to reference Green MR, Monti S, Rodig SJ, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010;116(17):3268–77.PubMedPubMedCentralCrossRef Green MR, Monti S, Rodig SJ, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010;116(17):3268–77.PubMedPubMedCentralCrossRef
30.
go back to reference Chen M, Pockaj B, Andreozzi M, et al. JAK2 and PD-L1 amplification enhance the dynamic expression of PD-L1 in Triple-negative breast Cancer. Clin Breast Cancer. 2019;19(1):87–8. Chen M, Pockaj B, Andreozzi M, et al. JAK2 and PD-L1 amplification enhance the dynamic expression of PD-L1 in Triple-negative breast Cancer. Clin Breast Cancer. 2019;19(1):87–8.
31.
go back to reference Sasidharan Nair V, Toor SM, Ali BR, Elkord E. Dual inhibition of STAT1 and STAT3 activation downregulates expression of PD-L1 in human breast cancer cells. Expert Opin Ther Targets. 2018;22(6):547–57.PubMedCrossRef Sasidharan Nair V, Toor SM, Ali BR, Elkord E. Dual inhibition of STAT1 and STAT3 activation downregulates expression of PD-L1 in human breast cancer cells. Expert Opin Ther Targets. 2018;22(6):547–57.PubMedCrossRef
32.
go back to reference Hogg SJ, Vervoort SJ, Deswal S, et al. BET-Bromodomain inhibitors engage the host Immune System and regulate expression of the Immune checkpoint ligand PD-L1. Cell Rep. 2017;18(9):2162–74.PubMedPubMedCentralCrossRef Hogg SJ, Vervoort SJ, Deswal S, et al. BET-Bromodomain inhibitors engage the host Immune System and regulate expression of the Immune checkpoint ligand PD-L1. Cell Rep. 2017;18(9):2162–74.PubMedPubMedCentralCrossRef
33.
go back to reference Lu C, Paschall AV, Shi H, et al. The MLL1-H3K4me3 Axis-mediated PD-L1 expression and pancreatic Cancer Immune Evasion. J Natl Cancer Inst. 2017;109(6):djw283.PubMedPubMedCentralCrossRef Lu C, Paschall AV, Shi H, et al. The MLL1-H3K4me3 Axis-mediated PD-L1 expression and pancreatic Cancer Immune Evasion. J Natl Cancer Inst. 2017;109(6):djw283.PubMedPubMedCentralCrossRef
34.
35.
go back to reference Chen L, Gibbons DL, Goswami S, et al. Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun. 2014;5:5241.PubMedCrossRef Chen L, Gibbons DL, Goswami S, et al. Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun. 2014;5:5241.PubMedCrossRef
37.
go back to reference Yang L, Cai Y, Zhang D, et al. miR-195/miR-497 regulate CD274 expression of Immune Regulatory ligands in Triple-negative breast Cancer. J Breast Cancer. 2018;21(4):371–81.PubMedPubMedCentralCrossRef Yang L, Cai Y, Zhang D, et al. miR-195/miR-497 regulate CD274 expression of Immune Regulatory ligands in Triple-negative breast Cancer. J Breast Cancer. 2018;21(4):371–81.PubMedPubMedCentralCrossRef
38.
39.
43.
go back to reference Garcia-Diaz A, Shin DS, Moreno BH, et al. Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep. 2017;19(6):1189–201.PubMedPubMedCentralCrossRef Garcia-Diaz A, Shin DS, Moreno BH, et al. Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep. 2017;19(6):1189–201.PubMedPubMedCentralCrossRef
44.
go back to reference Zerdes I, Wallerius M, Sifakis EG, et al. STAT3 activity promotes programmed-death Ligand 1 expression and suppresses Immune responses in breast Cancer. Cancers (Basel). 2019;11(10):1479.PubMedCrossRef Zerdes I, Wallerius M, Sifakis EG, et al. STAT3 activity promotes programmed-death Ligand 1 expression and suppresses Immune responses in breast Cancer. Cancers (Basel). 2019;11(10):1479.PubMedCrossRef
45.
go back to reference Liu M, Wei F, Wang J, et al. Myeloid-derived suppressor cells regulate the immunosuppressive functions of PD-1-PD-L1 + bregs through PD-L1/PI3K/AKT/NF-κB axis in breast cancer. Cell Death Dis. 2021;12(5):465.PubMedPubMedCentralCrossRef Liu M, Wei F, Wang J, et al. Myeloid-derived suppressor cells regulate the immunosuppressive functions of PD-1-PD-L1 + bregs through PD-L1/PI3K/AKT/NF-κB axis in breast cancer. Cell Death Dis. 2021;12(5):465.PubMedPubMedCentralCrossRef
46.
go back to reference Li Z, Zhou J, Zhang J, Li S, Wang H, Du J. Cancer-associated fibroblasts promote PD-L1 expression in mice cancer cells via secreting CXCL5. Int J Cancer. 2019;145(7):1946–57.PubMedPubMedCentralCrossRef Li Z, Zhou J, Zhang J, Li S, Wang H, Du J. Cancer-associated fibroblasts promote PD-L1 expression in mice cancer cells via secreting CXCL5. Int J Cancer. 2019;145(7):1946–57.PubMedPubMedCentralCrossRef
47.
go back to reference Segovia-Mendoza M, Romero-Garcia S, Lemini C, Prado-Garcia H. Determining factors in the therapeutic success of checkpoint immunotherapies against PD-L1 in breast Cancer: a focus on epithelial-mesenchymal transition activation. J Immunol Res. 2021;2021:6668573.PubMedPubMedCentralCrossRef Segovia-Mendoza M, Romero-Garcia S, Lemini C, Prado-Garcia H. Determining factors in the therapeutic success of checkpoint immunotherapies against PD-L1 in breast Cancer: a focus on epithelial-mesenchymal transition activation. J Immunol Res. 2021;2021:6668573.PubMedPubMedCentralCrossRef
48.
go back to reference Almozyan S, Colak D, Mansour F, et al. PD-L1 promotes OCT4 and nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation. Int J Cancer. 2017;141(7):1402–12.PubMedPubMedCentralCrossRef Almozyan S, Colak D, Mansour F, et al. PD-L1 promotes OCT4 and nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation. Int J Cancer. 2017;141(7):1402–12.PubMedPubMedCentralCrossRef
49.
go back to reference Tanaka T, Kutomi G, Kajiwara T, et al. Cancer-associated oxidoreductase ERO1-α promotes immune escape through up-regulation of PD-L1 in human breast cancer. Oncotarget. 2017;8(15):24706–18.PubMedPubMedCentralCrossRef Tanaka T, Kutomi G, Kajiwara T, et al. Cancer-associated oxidoreductase ERO1-α promotes immune escape through up-regulation of PD-L1 in human breast cancer. Oncotarget. 2017;8(15):24706–18.PubMedPubMedCentralCrossRef
50.
go back to reference Dohlman AB, Klug J, Mesko M, et al. A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors. Cell. 2022;185(20):3807–22.PubMedPubMedCentralCrossRef Dohlman AB, Klug J, Mesko M, et al. A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors. Cell. 2022;185(20):3807–22.PubMedPubMedCentralCrossRef
51.
go back to reference Fu A, Yao B, Dong T, et al. Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer. Cell. 2022;185(8):1356–e137226.PubMedCrossRef Fu A, Yao B, Dong T, et al. Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer. Cell. 2022;185(8):1356–e137226.PubMedCrossRef
52.
go back to reference Teng Y, Mu J, Xu F, et al. Gut bacterial isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death. Cell Host Microbe. 2022;30(7):944–60.PubMedPubMedCentralCrossRef Teng Y, Mu J, Xu F, et al. Gut bacterial isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death. Cell Host Microbe. 2022;30(7):944–60.PubMedPubMedCentralCrossRef
53.
54.
go back to reference Helmink BA, Khan MAW, Hermann A, Gopalakrishnan V, Wargo JA. The microbiome, cancer, and cancer therapy. Nat Med. 2019;25(3):377–88.PubMedCrossRef Helmink BA, Khan MAW, Hermann A, Gopalakrishnan V, Wargo JA. The microbiome, cancer, and cancer therapy. Nat Med. 2019;25(3):377–88.PubMedCrossRef
55.
go back to reference Jenkins S, Wesolowski R, Gatti-Mays ME. Improving breast Cancer responses to Immunotherapy-a search for the Achilles Heel of the Tumor Microenvironment. Curr Oncol Rep. 2021;23(5):55.PubMedCrossRef Jenkins S, Wesolowski R, Gatti-Mays ME. Improving breast Cancer responses to Immunotherapy-a search for the Achilles Heel of the Tumor Microenvironment. Curr Oncol Rep. 2021;23(5):55.PubMedCrossRef
56.
go back to reference Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259–71.PubMedCrossRef Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259–71.PubMedCrossRef
57.
go back to reference Barroso-Sousa R, Barry WT, Guo H, et al. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Ann Oncol. 2019;30(4):575–81.PubMedPubMedCentralCrossRef Barroso-Sousa R, Barry WT, Guo H, et al. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Ann Oncol. 2019;30(4):575–81.PubMedPubMedCentralCrossRef
58.
go back to reference Fang D, Zhu J. Dynamic balance between master transcription factors determines the fates and functions of CD4 T cell and innate lymphoid cell subsets. J Exp Med. 2017;214(7):1861–76.PubMedPubMedCentralCrossRef Fang D, Zhu J. Dynamic balance between master transcription factors determines the fates and functions of CD4 T cell and innate lymphoid cell subsets. J Exp Med. 2017;214(7):1861–76.PubMedPubMedCentralCrossRef
59.
go back to reference Gu-Trantien C, Loi S, Garaud S, et al. CD4⁺ follicular helper T cell infiltration predicts breast cancer survival. J Clin Invest. 2013;123(7):2873–92.PubMedPubMedCentralCrossRef Gu-Trantien C, Loi S, Garaud S, et al. CD4⁺ follicular helper T cell infiltration predicts breast cancer survival. J Clin Invest. 2013;123(7):2873–92.PubMedPubMedCentralCrossRef
60.
go back to reference Rozenblit M, Huang R, Danziger N, et al. Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers. J Immunother Cancer. 2020;8(2):e001558.PubMedPubMedCentralCrossRef Rozenblit M, Huang R, Danziger N, et al. Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers. J Immunother Cancer. 2020;8(2):e001558.PubMedPubMedCentralCrossRef
61.
go back to reference Pellegrino B, Tommasi C, Serra O, et al. Randomized, open-label, phase II, biomarker study of immune-mediated mechanism of action of neoadjuvant subcutaneous trastuzumab in patients with locally advanced, inflammatory, or early HER2-positive breast cancer-Immun-HER trial (GOIRC-01-2016). J Immunother Cancer. 2023;11(11):e007667.PubMedPubMedCentralCrossRef Pellegrino B, Tommasi C, Serra O, et al. Randomized, open-label, phase II, biomarker study of immune-mediated mechanism of action of neoadjuvant subcutaneous trastuzumab in patients with locally advanced, inflammatory, or early HER2-positive breast cancer-Immun-HER trial (GOIRC-01-2016). J Immunother Cancer. 2023;11(11):e007667.PubMedPubMedCentralCrossRef
62.
go back to reference Blomberg OS, Spagnuolo L, Garner H, et al. IL-5-producing CD4 + T cells and eosinophils cooperate to enhance response to immune checkpoint blockade in breast cancer. Cancer Cell. 2023;41(1):106–23.PubMedCrossRef Blomberg OS, Spagnuolo L, Garner H, et al. IL-5-producing CD4 + T cells and eosinophils cooperate to enhance response to immune checkpoint blockade in breast cancer. Cancer Cell. 2023;41(1):106–23.PubMedCrossRef
63.
go back to reference Zhang Y, Chen H, Mo H, et al. Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple-negative breast cancer. Cancer Cell. 2021;39(12):1578–93.PubMedCrossRef Zhang Y, Chen H, Mo H, et al. Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple-negative breast cancer. Cancer Cell. 2021;39(12):1578–93.PubMedCrossRef
64.
go back to reference Chang K, Jiao Y, Zhang B, et al. MGP + and IDO1 + tumor-associated macrophages facilitate immunoresistance in breast cancer revealed by single-cell RNA sequencing. Int Immunopharmacol. 2024;131:111818.PubMedCrossRef Chang K, Jiao Y, Zhang B, et al. MGP + and IDO1 + tumor-associated macrophages facilitate immunoresistance in breast cancer revealed by single-cell RNA sequencing. Int Immunopharmacol. 2024;131:111818.PubMedCrossRef
65.
go back to reference Emens LA, Molinero L, Loi S, et al. Atezolizumab and nab-Paclitaxel in Advanced Triple-negative breast Cancer: biomarker evaluation of the IMpassion130 study. J Natl Cancer Inst. 2021;113(8):1005–16.PubMedPubMedCentralCrossRef Emens LA, Molinero L, Loi S, et al. Atezolizumab and nab-Paclitaxel in Advanced Triple-negative breast Cancer: biomarker evaluation of the IMpassion130 study. J Natl Cancer Inst. 2021;113(8):1005–16.PubMedPubMedCentralCrossRef
66.
go back to reference Park JH, Jonas SF, Bataillon G, et al. Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy. Ann Oncol. 2019;30(12):1941–9.PubMedCrossRef Park JH, Jonas SF, Bataillon G, et al. Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy. Ann Oncol. 2019;30(12):1941–9.PubMedCrossRef
67.
go back to reference Denkert C, von Minckwitz G, Darb-Esfahani S, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.PubMedCrossRef Denkert C, von Minckwitz G, Darb-Esfahani S, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.PubMedCrossRef
68.
go back to reference Ingold Heppner B, Untch M, Denkert C, et al. Tumor-infiltrating lymphocytes: a predictive and prognostic biomarker in Neoadjuvant-treated HER2-Positive breast Cancer. Clin Cancer Res. 2016;22(23):5747–54.PubMedCrossRef Ingold Heppner B, Untch M, Denkert C, et al. Tumor-infiltrating lymphocytes: a predictive and prognostic biomarker in Neoadjuvant-treated HER2-Positive breast Cancer. Clin Cancer Res. 2016;22(23):5747–54.PubMedCrossRef
69.
go back to reference Byrne A, Savas P, Sant S, et al. Tissue-resident memory T cells in breast cancer control and immunotherapy responses. Nat Rev Clin Oncol. 2020;17(6):341–8.PubMedCrossRef Byrne A, Savas P, Sant S, et al. Tissue-resident memory T cells in breast cancer control and immunotherapy responses. Nat Rev Clin Oncol. 2020;17(6):341–8.PubMedCrossRef
70.
go back to reference Duhen T, Duhen R, Montler R, et al. Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. Nat Commun. 2018;9(1):2724.PubMedPubMedCentralCrossRef Duhen T, Duhen R, Montler R, et al. Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. Nat Commun. 2018;9(1):2724.PubMedPubMedCentralCrossRef
71.
go back to reference Murphy EM, Kelly AK, O’Meara C, Eivers B, Lonergan P, Fair S. Influence of bull age, ejaculate number, and season of collection on semen production and sperm motility parameters in Holstein Friesian bulls in a commercial artificial insemination centre. J Anim Sci. 2018;96(6):2408–18.PubMedPubMedCentralCrossRef Murphy EM, Kelly AK, O’Meara C, Eivers B, Lonergan P, Fair S. Influence of bull age, ejaculate number, and season of collection on semen production and sperm motility parameters in Holstein Friesian bulls in a commercial artificial insemination centre. J Anim Sci. 2018;96(6):2408–18.PubMedPubMedCentralCrossRef
72.
go back to reference Liu X, Tsang JYS, Hlaing T, et al. Distinct tertiary lymphoid structure associations and their prognostic relevance in HER2 positive and negative breast cancers. Oncologist. 2017;22(11):1316–24.PubMedPubMedCentralCrossRef Liu X, Tsang JYS, Hlaing T, et al. Distinct tertiary lymphoid structure associations and their prognostic relevance in HER2 positive and negative breast cancers. Oncologist. 2017;22(11):1316–24.PubMedPubMedCentralCrossRef
73.
go back to reference Wolf DM, Yau C, Wulfkuhle J, et al. Redefining breast cancer subtypes to guide treatment prioritization and maximize response: predictive biomarkers across 10 cancer therapies. Cancer Cell. 2022;40(6):609–23.PubMedPubMedCentralCrossRef Wolf DM, Yau C, Wulfkuhle J, et al. Redefining breast cancer subtypes to guide treatment prioritization and maximize response: predictive biomarkers across 10 cancer therapies. Cancer Cell. 2022;40(6):609–23.PubMedPubMedCentralCrossRef
74.
75.
go back to reference Karnik T, Kimler BF, Fan F, Tawfik O. PD-L1 in breast cancer: comparative analysis of 3 different antibodies. Hum Pathol. 2018;72:28–34.PubMedCrossRef Karnik T, Kimler BF, Fan F, Tawfik O. PD-L1 in breast cancer: comparative analysis of 3 different antibodies. Hum Pathol. 2018;72:28–34.PubMedCrossRef
76.
go back to reference Rom-Jurek EM, Kirchhammer N, Ugocsai P, Ortmann O, Wege AK, Brockhoff G. Regulation of programmed death Ligand 1 (PD-L1) expression in breast Cancer cell lines in Vitro and in Immunodeficient and Humanized Tumor mice. Int J Mol Sci. 2018;19(2):563.PubMedPubMedCentralCrossRef Rom-Jurek EM, Kirchhammer N, Ugocsai P, Ortmann O, Wege AK, Brockhoff G. Regulation of programmed death Ligand 1 (PD-L1) expression in breast Cancer cell lines in Vitro and in Immunodeficient and Humanized Tumor mice. Int J Mol Sci. 2018;19(2):563.PubMedPubMedCentralCrossRef
77.
78.
go back to reference Gupta S, Vanderbilt CM, Cotzia P, et al. Next-generation sequencing-based Assessment of JAK2, PD-L1, and PD-L2 Copy Number alterations at 9p24.1 in breast Cancer: potential implications for Clinical Management. J Mol Diagn. 2019;21(2):307–17.PubMedPubMedCentralCrossRef Gupta S, Vanderbilt CM, Cotzia P, et al. Next-generation sequencing-based Assessment of JAK2, PD-L1, and PD-L2 Copy Number alterations at 9p24.1 in breast Cancer: potential implications for Clinical Management. J Mol Diagn. 2019;21(2):307–17.PubMedPubMedCentralCrossRef
79.
80.
go back to reference Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8.PubMedPubMedCentralCrossRef Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8.PubMedPubMedCentralCrossRef
81.
go back to reference Van Allen EM, Miao D, Schilling B, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2016;352(6283):aaf8264. Van Allen EM, Miao D, Schilling B, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2016;352(6283):aaf8264.
83.
go back to reference Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21(10):1353–65.PubMedCrossRef Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21(10):1353–65.PubMedCrossRef
84.
go back to reference Thomas A, Routh ED, Pullikuth A, et al. Tumor mutational burden is a determinant of immune-mediated survival in breast cancer. Oncoimmunology. 2018;7(10):e1490854.PubMedPubMedCentralCrossRef Thomas A, Routh ED, Pullikuth A, et al. Tumor mutational burden is a determinant of immune-mediated survival in breast cancer. Oncoimmunology. 2018;7(10):e1490854.PubMedPubMedCentralCrossRef
85.
go back to reference Barroso-Sousa R, Keenan TE, Pernas S, et al. Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 blockade in metastatic triple-negative breast Cancer. Clin Cancer Res. 2020;26(11):2565–72.PubMedPubMedCentralCrossRef Barroso-Sousa R, Keenan TE, Pernas S, et al. Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 blockade in metastatic triple-negative breast Cancer. Clin Cancer Res. 2020;26(11):2565–72.PubMedPubMedCentralCrossRef
86.
go back to reference Barroso-Sousa R, Jain E, Cohen O, et al. Prevalence and mutational determinants of high tumor mutation burden in breast cancer. Ann Oncol. 2020;31(3):387–94.PubMedCrossRef Barroso-Sousa R, Jain E, Cohen O, et al. Prevalence and mutational determinants of high tumor mutation burden in breast cancer. Ann Oncol. 2020;31(3):387–94.PubMedCrossRef
87.
go back to reference Loibl S, Untch M, Burchardi N, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2022;33(7):743–4.PubMedCrossRef Loibl S, Untch M, Burchardi N, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2022;33(7):743–4.PubMedCrossRef
88.
go back to reference McGrail DJ, Pilié PG, Rashid NU, et al. High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types. Ann Oncol. 2021;32(5):661–72.PubMedCrossRef McGrail DJ, Pilié PG, Rashid NU, et al. High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types. Ann Oncol. 2021;32(5):661–72.PubMedCrossRef
89.
go back to reference Davoli T, Uno H, Wooten EC, Elledge SJ. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science. 2017;355(6322):eaaf8399.PubMedPubMedCentralCrossRef Davoli T, Uno H, Wooten EC, Elledge SJ. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science. 2017;355(6322):eaaf8399.PubMedPubMedCentralCrossRef
90.
go back to reference Liu L, Bai X, Wang J, et al. Combination of TMB and CNA Stratifies Prognostic and predictive responses to Immunotherapy Across Metastatic Cancer. Clin Cancer Res. 2019;25(24):7413–23.PubMedCrossRef Liu L, Bai X, Wang J, et al. Combination of TMB and CNA Stratifies Prognostic and predictive responses to Immunotherapy Across Metastatic Cancer. Clin Cancer Res. 2019;25(24):7413–23.PubMedCrossRef
91.
go back to reference Han Y, Wang J, Sun T, et al. Predictive biomarkers of response and survival following immunotherapy with a PD-L1 inhibitor benmelstobart (TQB2450) and antiangiogenic therapy with a VEGFR inhibitor anlotinib for pretreated advanced triple negative breast cancer. Signal Transduct Target Ther. 2023;8(1):429.PubMedPubMedCentralCrossRef Han Y, Wang J, Sun T, et al. Predictive biomarkers of response and survival following immunotherapy with a PD-L1 inhibitor benmelstobart (TQB2450) and antiangiogenic therapy with a VEGFR inhibitor anlotinib for pretreated advanced triple negative breast cancer. Signal Transduct Target Ther. 2023;8(1):429.PubMedPubMedCentralCrossRef
93.
94.
go back to reference Prasad V, Kaestner V, Mailankody S. Cancer drugs approved based on biomarkers and not Tumor Type-FDA approval of Pembrolizumab for Mismatch Repair-Deficient Solid cancers. JAMA Oncol. 2018;4(10):1439.PubMedCrossRef Prasad V, Kaestner V, Mailankody S. Cancer drugs approved based on biomarkers and not Tumor Type-FDA approval of Pembrolizumab for Mismatch Repair-Deficient Solid cancers. JAMA Oncol. 2018;4(10):1439.PubMedCrossRef
95.
go back to reference Fremd C, Hlevnjak M, Zapatka M, et al. Mismatch Repair Deficiency drives durable complete remission by targeting programmed death receptor 1 in a metastatic luminal breast Cancer patient. Breast Care (Basel). 2019;14(1):53–9.PubMedCrossRef Fremd C, Hlevnjak M, Zapatka M, et al. Mismatch Repair Deficiency drives durable complete remission by targeting programmed death receptor 1 in a metastatic luminal breast Cancer patient. Breast Care (Basel). 2019;14(1):53–9.PubMedCrossRef
96.
go back to reference Li A, Goodyear S, Fuss C, Mitri Z. Exceptional response to Pembrolizumab and Trastuzumab in a heavily pretreated patient with HER2-Positive TMB-H and MSI-H metastatic breast Cancer. JCO Precis Oncol. 2021;5:904–9.PubMedCrossRef Li A, Goodyear S, Fuss C, Mitri Z. Exceptional response to Pembrolizumab and Trastuzumab in a heavily pretreated patient with HER2-Positive TMB-H and MSI-H metastatic breast Cancer. JCO Precis Oncol. 2021;5:904–9.PubMedCrossRef
97.
go back to reference Ayers M, Lunceford J, Nebozhyn M, et al. IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017;127(8):2930–40.PubMedPubMedCentralCrossRef Ayers M, Lunceford J, Nebozhyn M, et al. IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017;127(8):2930–40.PubMedPubMedCentralCrossRef
98.
go back to reference Castro F, Cardoso AP, Gonçalves RM, Serre K, Oliveira MJ. Interferon-Gamma at the crossroads of Tumor Immune Surveillance or Evasion. Front Immunol. 2018;9:847.PubMedPubMedCentralCrossRef Castro F, Cardoso AP, Gonçalves RM, Serre K, Oliveira MJ. Interferon-Gamma at the crossroads of Tumor Immune Surveillance or Evasion. Front Immunol. 2018;9:847.PubMedPubMedCentralCrossRef
99.
go back to reference Bald T, Landsberg J, Lopez-Ramos D, et al. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. Cancer Discov. 2014;4(6):674–87.PubMedCrossRef Bald T, Landsberg J, Lopez-Ramos D, et al. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. Cancer Discov. 2014;4(6):674–87.PubMedCrossRef
100.
go back to reference Ott PA, Bang YJ, Piha-Paul SA, et al. T-Cell-inflamed gene-expression Profile, programmed death Ligand 1 expression, and Tumor Mutational Burden Predict Efficacy in patients treated with Pembrolizumab Across 20 cancers: KEYNOTE-028. J Clin Oncol. 2019;37(4):318–27.PubMedCrossRef Ott PA, Bang YJ, Piha-Paul SA, et al. T-Cell-inflamed gene-expression Profile, programmed death Ligand 1 expression, and Tumor Mutational Burden Predict Efficacy in patients treated with Pembrolizumab Across 20 cancers: KEYNOTE-028. J Clin Oncol. 2019;37(4):318–27.PubMedCrossRef
101.
go back to reference Danaher P, Warren S, Lu R, et al. Pan-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from the Cancer Genome Atlas (TCGA). J Immunother Cancer. 2018;6(1):63.PubMedPubMedCentralCrossRef Danaher P, Warren S, Lu R, et al. Pan-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from the Cancer Genome Atlas (TCGA). J Immunother Cancer. 2018;6(1):63.PubMedPubMedCentralCrossRef
102.
go back to reference Cristescu R, Mogg R, Ayers M, et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science. 2019;363(6430):eaax1384. Cristescu R, Mogg R, Ayers M, et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science. 2019;363(6430):eaax1384.
103.
go back to reference Hugo W, Zaretsky JM, Sun L, et al. Genomic and transcriptomic features of response to Anti-PD-1 therapy in metastatic melanoma. Cell. 2017;168(3):542.PubMedCrossRef Hugo W, Zaretsky JM, Sun L, et al. Genomic and transcriptomic features of response to Anti-PD-1 therapy in metastatic melanoma. Cell. 2017;168(3):542.PubMedCrossRef
104.
go back to reference Hollern DP, Xu N, Thennavan A, et al. B cells and T Follicular Helper Cells Mediate Response to checkpoint inhibitors in high mutation Burden mouse models of breast Cancer. Cell. 2019;179(5):1191–206.PubMedPubMedCentralCrossRef Hollern DP, Xu N, Thennavan A, et al. B cells and T Follicular Helper Cells Mediate Response to checkpoint inhibitors in high mutation Burden mouse models of breast Cancer. Cell. 2019;179(5):1191–206.PubMedPubMedCentralCrossRef
105.
go back to reference Zhao F, Zhao C, Xu T, et al. Single-cell and bulk RNA sequencing analysis of B cell marker genes in TNBC TME landscape and immunotherapy. Front Immunol. 2023;14:1245514.PubMedPubMedCentralCrossRef Zhao F, Zhao C, Xu T, et al. Single-cell and bulk RNA sequencing analysis of B cell marker genes in TNBC TME landscape and immunotherapy. Front Immunol. 2023;14:1245514.PubMedPubMedCentralCrossRef
106.
go back to reference Shi Z, Shen J, Qiu J, Zhao Q, Hua K, Wang H. CXCL10 potentiates immune checkpoint blockade therapy in homologous recombination-deficient tumors. Theranostics. 2021;11(15):7175–87.PubMedPubMedCentralCrossRef Shi Z, Shen J, Qiu J, Zhao Q, Hua K, Wang H. CXCL10 potentiates immune checkpoint blockade therapy in homologous recombination-deficient tumors. Theranostics. 2021;11(15):7175–87.PubMedPubMedCentralCrossRef
107.
go back to reference Wan JCM, Massie C, Garcia-Corbacho J, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223–38.PubMedCrossRef Wan JCM, Massie C, Garcia-Corbacho J, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223–38.PubMedCrossRef
108.
go back to reference Cabel L, Proudhon C, Romano E, et al. Clinical potential of circulating tumour DNA in patients receiving anticancer immunotherapy. Nat Rev Clin Oncol. 2018;15(10):639–50.PubMedCrossRef Cabel L, Proudhon C, Romano E, et al. Clinical potential of circulating tumour DNA in patients receiving anticancer immunotherapy. Nat Rev Clin Oncol. 2018;15(10):639–50.PubMedCrossRef
109.
go back to reference Georgiadis A, Durham JN, Keefer LA, et al. Noninvasive Detection of Microsatellite Instability and high Tumor Mutation Burden in Cancer patients treated with PD-1 blockade. Clin Cancer Res. 2019;25(23):7024–34.PubMedPubMedCentralCrossRef Georgiadis A, Durham JN, Keefer LA, et al. Noninvasive Detection of Microsatellite Instability and high Tumor Mutation Burden in Cancer patients treated with PD-1 blockade. Clin Cancer Res. 2019;25(23):7024–34.PubMedPubMedCentralCrossRef
110.
go back to reference Bratman SV, Yang SYC, Iafolla MAJ, et al. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat Cancer. 2020;1(9):873–81.PubMedCrossRef Bratman SV, Yang SYC, Iafolla MAJ, et al. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat Cancer. 2020;1(9):873–81.PubMedCrossRef
111.
go back to reference Barth DA, Stanzer S, Spiegelberg JA, et al. Patterns of peripheral blood B-Cell subtypes are Associated with Treatment response in patients treated with Immune Checkpoint inhibitors: a prospective longitudinal Pan-cancer Study. Front Immunol. 2022;13:840207.PubMedPubMedCentralCrossRef Barth DA, Stanzer S, Spiegelberg JA, et al. Patterns of peripheral blood B-Cell subtypes are Associated with Treatment response in patients treated with Immune Checkpoint inhibitors: a prospective longitudinal Pan-cancer Study. Front Immunol. 2022;13:840207.PubMedPubMedCentralCrossRef
112.
go back to reference Dyikanov D, Zaitsev A, Vasileva T, et al. Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in patients with cancer. Cancer Cell. 2024;42(5):759–79.PubMedCrossRef Dyikanov D, Zaitsev A, Vasileva T, et al. Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in patients with cancer. Cancer Cell. 2024;42(5):759–79.PubMedCrossRef
113.
go back to reference Massa C, Karn T, Weber K et al. Abstract PD9-04: immunological and clinical consequences of durvalumab treatment in combination to neoadjuvant chemotherapy in triple-negative breast cancer patients. Cancer Res. 2023;83 PD9-04-PD9-04. Massa C, Karn T, Weber K et al. Abstract PD9-04: immunological and clinical consequences of durvalumab treatment in combination to neoadjuvant chemotherapy in triple-negative breast cancer patients. Cancer Res. 2023;83 PD9-04-PD9-04.
114.
go back to reference Ghebeh H, Elshenawy MA, AlSayed AD, Al-Tweigeri T. Peripheral blood eosinophil count is associated with response to chemoimmunotherapy in metastatic triple-negative breast cancer. Immunotherapy. 2022;14(4):189–99.PubMedCrossRef Ghebeh H, Elshenawy MA, AlSayed AD, Al-Tweigeri T. Peripheral blood eosinophil count is associated with response to chemoimmunotherapy in metastatic triple-negative breast cancer. Immunotherapy. 2022;14(4):189–99.PubMedCrossRef
115.
go back to reference Zuazo M, Arasanz H, Fernández-Hinojal G, et al. Functional systemic CD4 immunity is required for clinical responses to PD-L1/PD-1 blockade therapy. EMBO Mol Med. 2019;11(7):e10293.PubMedPubMedCentralCrossRef Zuazo M, Arasanz H, Fernández-Hinojal G, et al. Functional systemic CD4 immunity is required for clinical responses to PD-L1/PD-1 blockade therapy. EMBO Mol Med. 2019;11(7):e10293.PubMedPubMedCentralCrossRef
116.
go back to reference Allen BM, Hiam KJ, Burnett CE, et al. Systemic dysfunction and plasticity of the immune macroenvironment in cancer models. Nat Med. 2024;30(5):1502.PubMedCrossRef Allen BM, Hiam KJ, Burnett CE, et al. Systemic dysfunction and plasticity of the immune macroenvironment in cancer models. Nat Med. 2024;30(5):1502.PubMedCrossRef
117.
118.
go back to reference Gravett AM, Trautwein N, Stevanović S, Dalgleish AG, Copier J. Gemcitabine alters the proteasome composition and immunopeptidome of tumour cells. Oncoimmunology. 2018;7(6):e1438107.PubMedPubMedCentralCrossRef Gravett AM, Trautwein N, Stevanović S, Dalgleish AG, Copier J. Gemcitabine alters the proteasome composition and immunopeptidome of tumour cells. Oncoimmunology. 2018;7(6):e1438107.PubMedPubMedCentralCrossRef
119.
go back to reference Buhtoiarov IN, Sondel PM, Wigginton JM, et al. Anti-tumour synergy of cytotoxic chemotherapy and anti-CD40 plus CpG-ODN immunotherapy through repolarization of tumour-associated macrophages. Immunology. 2011;132(2):226–39.PubMedPubMedCentralCrossRef Buhtoiarov IN, Sondel PM, Wigginton JM, et al. Anti-tumour synergy of cytotoxic chemotherapy and anti-CD40 plus CpG-ODN immunotherapy through repolarization of tumour-associated macrophages. Immunology. 2011;132(2):226–39.PubMedPubMedCentralCrossRef
120.
go back to reference Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic Gr-1+/CD11b + myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res off J Am Assoc Cancer Res. 2005;11(18):6713–21.CrossRef Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic Gr-1+/CD11b + myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res off J Am Assoc Cancer Res. 2005;11(18):6713–21.CrossRef
121.
go back to reference Germano G, Frapolli R, Belgiovine C, Anselmo A, Pesce S, Liguori M, Erba E, Uboldi S, Zucchetti M, Pasqualini F, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell. 2013;23(2):249–62.PubMedCrossRef Germano G, Frapolli R, Belgiovine C, Anselmo A, Pesce S, Liguori M, Erba E, Uboldi S, Zucchetti M, Pasqualini F, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell. 2013;23(2):249–62.PubMedCrossRef
122.
go back to reference Dimeloe S, Frick C, Fischer M, Gubser PM, Razik L, Bantug GR, Ravon M, Langenkamp A, Hess C. Human regulatory T cells lack the cyclophosphamide-extruding transporter ABCB1 and are more susceptible to cyclophosphamide-induced apoptosis. Eur J Immunol. 2014;44(12):3614–20.PubMedCrossRef Dimeloe S, Frick C, Fischer M, Gubser PM, Razik L, Bantug GR, Ravon M, Langenkamp A, Hess C. Human regulatory T cells lack the cyclophosphamide-extruding transporter ABCB1 and are more susceptible to cyclophosphamide-induced apoptosis. Eur J Immunol. 2014;44(12):3614–20.PubMedCrossRef
123.
go back to reference Reits EA, Hodge JW, Herberts CA, et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med. 2006;203(5):1259–71.PubMedPubMedCentralCrossRef Reits EA, Hodge JW, Herberts CA, et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med. 2006;203(5):1259–71.PubMedPubMedCentralCrossRef
124.
go back to reference Gameiro SR, Jammeh ML, Wattenberg MM, Tsang KY, Ferrone S, Hodge JW. Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing. Oncotarget. 2014;5(2):403–16.PubMedCrossRef Gameiro SR, Jammeh ML, Wattenberg MM, Tsang KY, Ferrone S, Hodge JW. Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing. Oncotarget. 2014;5(2):403–16.PubMedCrossRef
125.
go back to reference Vermeer DW, Spanos WC, Vermeer PD, Bruns AM, Lee KM, Lee JH. Radiation-induced loss of cell surface CD47 enhances immune-mediated clearance of human papillomavirus-positive cancer. Int J Cancer. 2013;133(1):120–9.PubMedPubMedCentralCrossRef Vermeer DW, Spanos WC, Vermeer PD, Bruns AM, Lee KM, Lee JH. Radiation-induced loss of cell surface CD47 enhances immune-mediated clearance of human papillomavirus-positive cancer. Int J Cancer. 2013;133(1):120–9.PubMedPubMedCentralCrossRef
126.
go back to reference Spitz DR, Azzam EI, Li JJ, Gius D. Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: a unifying concept in stress response biology. Cancer Metastasis Rev. 2004;23(3–4):311–22.PubMedCrossRef Spitz DR, Azzam EI, Li JJ, Gius D. Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: a unifying concept in stress response biology. Cancer Metastasis Rev. 2004;23(3–4):311–22.PubMedCrossRef
127.
go back to reference Deng L, Liang H, Xu M, et al. STING-Dependent cytosolic DNA sensing promotes Radiation-Induced type I Interferon-Dependent Antitumor immunity in immunogenic tumors. Immunity. 2014;41(5):843–52.PubMedPubMedCentralCrossRef Deng L, Liang H, Xu M, et al. STING-Dependent cytosolic DNA sensing promotes Radiation-Induced type I Interferon-Dependent Antitumor immunity in immunogenic tumors. Immunity. 2014;41(5):843–52.PubMedPubMedCentralCrossRef
128.
go back to reference Jiang W, Chan CK, Weissman IL, Kim BYS, Hahn SM. Immune Priming of the Tumor Microenvironment by Radiation. Trends Cancer. 2016;2(11):638–45.PubMedCrossRef Jiang W, Chan CK, Weissman IL, Kim BYS, Hahn SM. Immune Priming of the Tumor Microenvironment by Radiation. Trends Cancer. 2016;2(11):638–45.PubMedCrossRef
129.
130.
go back to reference Kho VM, Mekers VE, Span PN, Bussink J, Adema GJ. Radiotherapy and cGAS/STING signaling: impact on MDSCs in the tumor microenvironment. Cell Immunol. 2021;362:104298.PubMedCrossRef Kho VM, Mekers VE, Span PN, Bussink J, Adema GJ. Radiotherapy and cGAS/STING signaling: impact on MDSCs in the tumor microenvironment. Cell Immunol. 2021;362:104298.PubMedCrossRef
131.
go back to reference Ugel S, De Sanctis F, Mandruzzato S, Bronte V. Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages. J Clin Invest. 2015;125(9):3365–76.PubMedPubMedCentralCrossRef Ugel S, De Sanctis F, Mandruzzato S, Bronte V. Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages. J Clin Invest. 2015;125(9):3365–76.PubMedPubMedCentralCrossRef
132.
go back to reference Zhang Z, Yang S, Wang Q. Impact of MET alterations on targeted therapy with EGFR-tyrosine kinase inhibitors for EGFR-mutant lung cancer. Biomark Res. 2019;7(1):27.PubMedPubMedCentralCrossRef Zhang Z, Yang S, Wang Q. Impact of MET alterations on targeted therapy with EGFR-tyrosine kinase inhibitors for EGFR-mutant lung cancer. Biomark Res. 2019;7(1):27.PubMedPubMedCentralCrossRef
133.
go back to reference Robert C, Ribas A, Hamid O, et al. Durable complete response after discontinuation of Pembrolizumab in patients with metastatic melanoma. J Clin Oncol. 2018;36(17):1668–74.PubMedCrossRef Robert C, Ribas A, Hamid O, et al. Durable complete response after discontinuation of Pembrolizumab in patients with metastatic melanoma. J Clin Oncol. 2018;36(17):1668–74.PubMedCrossRef
134.
go back to reference Pan CX, Zhang H, Tepper CG, et al. Development and characterization of bladder Cancer patient-derived xenografts for molecularly guided targeted therapy. PLoS ONE. 2015;10(8):e0134346.PubMedPubMedCentralCrossRef Pan CX, Zhang H, Tepper CG, et al. Development and characterization of bladder Cancer patient-derived xenografts for molecularly guided targeted therapy. PLoS ONE. 2015;10(8):e0134346.PubMedPubMedCentralCrossRef
135.
go back to reference Kaur S, Chang T, Singh SP, et al. CD47 signaling regulates the immunosuppressive activity of VEGF in T cells. J Immunol. 2014;193(8):3914–24.PubMedCrossRef Kaur S, Chang T, Singh SP, et al. CD47 signaling regulates the immunosuppressive activity of VEGF in T cells. J Immunol. 2014;193(8):3914–24.PubMedCrossRef
136.
go back to reference Ziogas AC, Gavalas NG, Tsiatas M, et al. VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor type 2. Int J Cancer. 2012;130(4):857–64.PubMedCrossRef Ziogas AC, Gavalas NG, Tsiatas M, et al. VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor type 2. Int J Cancer. 2012;130(4):857–64.PubMedCrossRef
137.
go back to reference Dubovsky JA, Beckwith KA, Natarajan G, Woyach JA, Jaglowski S, Zhong Y, Hessler JD, Liu TM, Chang BY, Larkin KM, et al. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013;122(15):2539–49.PubMedPubMedCentralCrossRef Dubovsky JA, Beckwith KA, Natarajan G, Woyach JA, Jaglowski S, Zhong Y, Hessler JD, Liu TM, Chang BY, Larkin KM, et al. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013;122(15):2539–49.PubMedPubMedCentralCrossRef
138.
go back to reference Chakraborty B, Byemerwa J, Shepherd J, et al. Inhibition of estrogen signaling in myeloid cells increases tumor immunity in melanoma. J Clin Invest. 2021;131(23):e151347.PubMedPubMedCentralCrossRef Chakraborty B, Byemerwa J, Shepherd J, et al. Inhibition of estrogen signaling in myeloid cells increases tumor immunity in melanoma. J Clin Invest. 2021;131(23):e151347.PubMedPubMedCentralCrossRef
139.
go back to reference Ali HR, Chlon L, Pharoah PD, Markowetz F, Caldas C. Patterns of Immune infiltration in breast Cancer and their clinical implications: a gene-expression-based retrospective study. PLoS Med. 2016;13(12):e1002194.PubMedPubMedCentralCrossRef Ali HR, Chlon L, Pharoah PD, Markowetz F, Caldas C. Patterns of Immune infiltration in breast Cancer and their clinical implications: a gene-expression-based retrospective study. PLoS Med. 2016;13(12):e1002194.PubMedPubMedCentralCrossRef
140.
go back to reference Artham S, Juras PK, Goyal A, et al. Estrogen signaling suppresses tumor-associated tissue eosinophilia to promote breast tumor growth. Sci Adv. 2024;10(39):eadp2442.PubMedPubMedCentralCrossRef Artham S, Juras PK, Goyal A, et al. Estrogen signaling suppresses tumor-associated tissue eosinophilia to promote breast tumor growth. Sci Adv. 2024;10(39):eadp2442.PubMedPubMedCentralCrossRef
141.
go back to reference Nagarsheth N, Wicha MS, Zou W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol. 2017;17(9):559–72.PubMedPubMedCentralCrossRef Nagarsheth N, Wicha MS, Zou W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol. 2017;17(9):559–72.PubMedPubMedCentralCrossRef
142.
go back to reference Almeida AR, Legrand N, Papiernik M, Freitas AA. Homeostasis of peripheral CD4 + T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4 + T cell numbers. J Immunol. 2002;169(9):4850–60.PubMedCrossRef Almeida AR, Legrand N, Papiernik M, Freitas AA. Homeostasis of peripheral CD4 + T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4 + T cell numbers. J Immunol. 2002;169(9):4850–60.PubMedCrossRef
143.
go back to reference Chen ML, Pittet MJ, Gorelik L, Flavell RA, Weissleder R, von Boehmer H, Khazaie K. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc Natl Acad Sci U S A. 2005;102(2):419–24.PubMedCrossRef Chen ML, Pittet MJ, Gorelik L, Flavell RA, Weissleder R, von Boehmer H, Khazaie K. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc Natl Acad Sci U S A. 2005;102(2):419–24.PubMedCrossRef
144.
go back to reference Hicks KC, Chariou PL, Ozawa Y, et al. Tumour-targeted interleukin-12 and entinostat combination therapy improves cancer survival by reprogramming the tumour immune cell landscape. Nat Commun. 2021;12(1):5151.PubMedPubMedCentralCrossRef Hicks KC, Chariou PL, Ozawa Y, et al. Tumour-targeted interleukin-12 and entinostat combination therapy improves cancer survival by reprogramming the tumour immune cell landscape. Nat Commun. 2021;12(1):5151.PubMedPubMedCentralCrossRef
145.
go back to reference Sidiropoulos DN, Rafie CI, Jang JK, et al. Entinostat decreases Immune suppression to promote antitumor responses in a HER2 + breast Tumor Microenvironment. Cancer Immunol Res. 2022;10(5):656–69.PubMedPubMedCentralCrossRef Sidiropoulos DN, Rafie CI, Jang JK, et al. Entinostat decreases Immune suppression to promote antitumor responses in a HER2 + breast Tumor Microenvironment. Cancer Immunol Res. 2022;10(5):656–69.PubMedPubMedCentralCrossRef
146.
go back to reference Naing A, Wong DJ, Infante JR, et al. Pegilodecakin combined with pembrolizumab or nivolumab for patients with advanced solid tumours (IVY): a multicentre, multicohort, open-label, phase 1b trial. Lancet Oncol. 2019;20(12):e663. Naing A, Wong DJ, Infante JR, et al. Pegilodecakin combined with pembrolizumab or nivolumab for patients with advanced solid tumours (IVY): a multicentre, multicohort, open-label, phase 1b trial. Lancet Oncol. 2019;20(12):e663.
147.
go back to reference Qin S, Li A, Yi M, Yu S, Zhang M, Wu K. Recent advances on anti-angiogenesis receptor tyrosine kinase inhibitors in cancer therapy. J Hematol Oncol. 2019;12(1):27.PubMedPubMedCentralCrossRef Qin S, Li A, Yi M, Yu S, Zhang M, Wu K. Recent advances on anti-angiogenesis receptor tyrosine kinase inhibitors in cancer therapy. J Hematol Oncol. 2019;12(1):27.PubMedPubMedCentralCrossRef
148.
149.
go back to reference LIU J, WANG Y. Multicenter phase II trial of Camrelizumab combined with apatinib and Eribulin in heavily pretreated patients with advanced triple-negative breast cancer. Nat Commun. 2022;13(1):3011.PubMedPubMedCentralCrossRef LIU J, WANG Y. Multicenter phase II trial of Camrelizumab combined with apatinib and Eribulin in heavily pretreated patients with advanced triple-negative breast cancer. Nat Commun. 2022;13(1):3011.PubMedPubMedCentralCrossRef
150.
go back to reference Li Q, Wang Y, Jia W, Low-Dose Anti-Angiogenic Therapy Sensitizes Breast Cancer to PD-1 Blockade. Clin Cancer Res., Q et al. Biomarkers of response to camrelizumab combined with apatinib: an analysis from a phase II trial in advanced triple-negative breast cancer patients. Breast Cancer Res Treat. 2021; 186(3);687-697. Li Q, Wang Y, Jia W, Low-Dose Anti-Angiogenic Therapy Sensitizes Breast Cancer to PD-1 Blockade. Clin Cancer Res., Q et al. Biomarkers of response to camrelizumab combined with apatinib: an analysis from a phase II trial in advanced triple-negative breast cancer patients. Breast Cancer Res Treat. 2021; 186(3);687-697.
151.
go back to reference Basu A, Hoerning A, Datta D, Edelbauer M, Stack MP, Calzadilla K, Pal S, Briscoe DM. Cutting edge: vascular endothelial growth factor-mediated signaling in human CD45RO + CD4 + T cells promotes akt and ERK activation and costimulates IFN-gamma production. J Immunol. 2010;184(2):545–9.PubMedCrossRef Basu A, Hoerning A, Datta D, Edelbauer M, Stack MP, Calzadilla K, Pal S, Briscoe DM. Cutting edge: vascular endothelial growth factor-mediated signaling in human CD45RO + CD4 + T cells promotes akt and ERK activation and costimulates IFN-gamma production. J Immunol. 2010;184(2):545–9.PubMedCrossRef
152.
go back to reference Nefedova Y, Huang M, Kusmartsev S, Bhattacharya R, Cheng P, Salup R, Jove R, Gabrilovich D. Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer. J Immunol. 2004;172(1):464–74.PubMedCrossRef Nefedova Y, Huang M, Kusmartsev S, Bhattacharya R, Cheng P, Salup R, Jove R, Gabrilovich D. Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer. J Immunol. 2004;172(1):464–74.PubMedCrossRef
153.
go back to reference Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med. 1996;2(10):1096–103.PubMedCrossRef Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med. 1996;2(10):1096–103.PubMedCrossRef
154.
go back to reference Almand B, Resser JR, Lindman B, Nadaf S, Clark JI, Kwon ED, Carbone DP, Gabrilovich DI. Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res off J Am Assoc Cancer Res. 2000;6(5):1755–66. Almand B, Resser JR, Lindman B, Nadaf S, Clark JI, Kwon ED, Carbone DP, Gabrilovich DI. Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res off J Am Assoc Cancer Res. 2000;6(5):1755–66.
155.
go back to reference Carnevalli LS, Sinclair C, Taylor MA, et al. PI3Kα/δ inhibition promotes anti-tumor immunity through direct enhancement of effector CD8 + T-cell activity. J Immunother Cancer. 2018;6(1):158.PubMedPubMedCentralCrossRef Carnevalli LS, Sinclair C, Taylor MA, et al. PI3Kα/δ inhibition promotes anti-tumor immunity through direct enhancement of effector CD8 + T-cell activity. J Immunother Cancer. 2018;6(1):158.PubMedPubMedCentralCrossRef
156.
go back to reference Liu X, Si F, Bagley D, et al. Blockades of effector T cell senescence and exhaustion synergistically enhance antitumor immunity and immunotherapy. J Immunother Cancer. 2022;10(10):e005020.PubMedPubMedCentralCrossRef Liu X, Si F, Bagley D, et al. Blockades of effector T cell senescence and exhaustion synergistically enhance antitumor immunity and immunotherapy. J Immunother Cancer. 2022;10(10):e005020.PubMedPubMedCentralCrossRef
157.
go back to reference Palakurthi B, Fross SR, Guldner IH, et al. Targeting CXCL16 and STAT1 augments immune checkpoint blockade therapy in triple-negative breast cancer. Nat Commun. 2023;14(1):2109.PubMedPubMedCentralCrossRef Palakurthi B, Fross SR, Guldner IH, et al. Targeting CXCL16 and STAT1 augments immune checkpoint blockade therapy in triple-negative breast cancer. Nat Commun. 2023;14(1):2109.PubMedPubMedCentralCrossRef
158.
go back to reference Miller KD, O’Connor S, Pniewski KA, et al. Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer. Nat Cancer. 2023;4(10):1491–507.PubMedPubMedCentralCrossRef Miller KD, O’Connor S, Pniewski KA, et al. Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer. Nat Cancer. 2023;4(10):1491–507.PubMedPubMedCentralCrossRef
159.
go back to reference Clift R, Souratha J, Garrovillo SA, Zimmerman S, Blouw B. Remodeling the Tumor Microenvironment sensitizes breast tumors to anti-programmed death-ligand 1 immunotherapy. Cancer Res. 2019;79(16):4149–59.PubMedCrossRef Clift R, Souratha J, Garrovillo SA, Zimmerman S, Blouw B. Remodeling the Tumor Microenvironment sensitizes breast tumors to anti-programmed death-ligand 1 immunotherapy. Cancer Res. 2019;79(16):4149–59.PubMedCrossRef
160.
go back to reference Sarkar OS, Donninger H, Al Rayyan N, et al. Monocytic MDSCs exhibit superior immune suppression via adenosine and depletion of adenosine improves efficacy of immunotherapy. Sci Adv. 2023;9(26):eadg3736.PubMedPubMedCentralCrossRef Sarkar OS, Donninger H, Al Rayyan N, et al. Monocytic MDSCs exhibit superior immune suppression via adenosine and depletion of adenosine improves efficacy of immunotherapy. Sci Adv. 2023;9(26):eadg3736.PubMedPubMedCentralCrossRef
161.
go back to reference Chung YM, Khan PP, Wang H, et al. Sensitizing tumors to anti-PD-1 therapy by promoting NK and CD8 + T cells via pharmacological activation of FOXO3. J Immunother Cancer. 2021;9(12):e002772.PubMedPubMedCentralCrossRef Chung YM, Khan PP, Wang H, et al. Sensitizing tumors to anti-PD-1 therapy by promoting NK and CD8 + T cells via pharmacological activation of FOXO3. J Immunother Cancer. 2021;9(12):e002772.PubMedPubMedCentralCrossRef
162.
go back to reference Li H, Xiao Y, Li Q, et al. The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1. Cancer Cell. 2022;40(1):36–52.PubMedCrossRef Li H, Xiao Y, Li Q, et al. The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1. Cancer Cell. 2022;40(1):36–52.PubMedCrossRef
163.
go back to reference Huang MY, Chen YC, Lyu WY, et al. Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8 + T cells via increasing intratumoral CXCL10. Pharmacol Res. 2023;198:106988.PubMedCrossRef Huang MY, Chen YC, Lyu WY, et al. Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8 + T cells via increasing intratumoral CXCL10. Pharmacol Res. 2023;198:106988.PubMedCrossRef
164.
go back to reference Magrì A, Germano G, Lorenzato A, et al. High-dose vitamin C enhances cancer immunotherapy. Sci Transl Med. 2020;12(532):eaay8707.PubMedCrossRef Magrì A, Germano G, Lorenzato A, et al. High-dose vitamin C enhances cancer immunotherapy. Sci Transl Med. 2020;12(532):eaay8707.PubMedCrossRef
165.
go back to reference Gandini S, Boniol M, Haukka J, et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2011;128(6):1414–24.PubMedCrossRef Gandini S, Boniol M, Haukka J, et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2011;128(6):1414–24.PubMedCrossRef
166.
go back to reference De Smedt J, Van Kelst S, Boecxstaens V, et al. Vitamin D supplementation in cutaneous malignant melanoma outcome (ViDMe): a randomized controlled trial. BMC Cancer. 2017;17(1):562.PubMedPubMedCentralCrossRef De Smedt J, Van Kelst S, Boecxstaens V, et al. Vitamin D supplementation in cutaneous malignant melanoma outcome (ViDMe): a randomized controlled trial. BMC Cancer. 2017;17(1):562.PubMedPubMedCentralCrossRef
167.
go back to reference Urashima M, Ohdaira H, Akutsu T, et al. Effect of vitamin D supplementation on Relapse-Free Survival among patients with Digestive Tract cancers: the AMATERASU Randomized Clinical Trial. JAMA. 2019;321(14):1361–9.PubMedPubMedCentralCrossRef Urashima M, Ohdaira H, Akutsu T, et al. Effect of vitamin D supplementation on Relapse-Free Survival among patients with Digestive Tract cancers: the AMATERASU Randomized Clinical Trial. JAMA. 2019;321(14):1361–9.PubMedPubMedCentralCrossRef
168.
Metadata
Title
PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies
Authors
Menglei Jin
Jun Fang
Junwen Peng
Xintian Wang
Ping Xing
Kunpeng Jia
Jianming Hu
Danting Wang
Yuxin Ding
Xinyu Wang
Wenlu Li
Zhigang Chen
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2024
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-024-02176-8
SPONSORED

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

In this webinar, Professor Martin Dreyling and an esteemed international panel of CAR T-cell therapy experts discuss the latest data on the safety, efficacy, and clinical impact of CAR T-cell therapies in the treatment of r/r DLBCL and r/r FL.

Please note, this webinar is not intended for healthcare professionals based in the US and UK.

Sponsored by:
  • Novartis Pharma AG
Chaired by: Prof. Martin Dreyling
Developed by: Springer Healthcare
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