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Journal of Cancer Research and Clinical Oncology

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Open Access 01-05-2024 | Colorectal Cancer | Review

Role played by MDSC in colitis-associated colorectal cancer and potential therapeutic strategies

Authors: Kang Wang, Yun Wang, Kai Yin

Published in: Journal of Cancer Research and Clinical Oncology | Issue 5/2024

Abstract

Colitis-associated colorectal cancer has been a hot topic in public health issues worldwide. Numerous studies have demonstrated the significance of myeloid-derived suppressor cells (MDSCs) in the progression of this ailment, but the specific mechanism of their role in the transformation of inflammation to cancer is unclear, and potential therapies targeting MDSC are also unclear. This paper outlines the possible involvement of MDSC to the development of colitis-associated colorectal cancer. It also explores the immune and other relevant roles played by MDSC, and collates relevant targeted therapies against MDSC. In addition, current targeted therapies for colorectal cancer are analyzed and summarized.

Akdeniz N, Kaplan MA, Uncu D, İnanç M, Kaya S, Dane F, Işıkdoğan A (2021) The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study. Int J Colorectal Dis 36(6):1311–1319. https://doi.org/10.1007/s00384-021-03888-9CrossRefPubMed

André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Diaz LA Jr (2020) Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med 383(23):2207–2218. https://doi.org/10.1056/NEJMoa2017699CrossRefPubMed

André T, Falcone A, Shparyk Y, Moiseenko F, Polo-Marques E, Csöszi T, Saunders MP (2023) Trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer ineligible for intensive therapy (SOLSTICE): a randomised, open-label phase 3 study. Lancet Gastroenterol Hepatol 8(2):133–144. https://doi.org/10.1016/s2468-1253(22)00334-xCrossRefPubMed

Bitsch R, Kurzay A, Özbay Kurt F, De La Torre C, Lasser S, Lepper A, Umansky V (2022) STAT3 inhibitor Napabucasin abrogates MDSC immunosuppressive capacity and prolongs survival of melanoma-bearing mice. J Immunother Cancer 10(3):e004384. https://doi.org/10.1136/jitc-2021-004384CrossRefPubMedPubMedCentral

Boige V, Blons H, François E, Ben Abdelghani M, Phelip JM, Le Brun-Ly V, Bouché O (2023) Maintenance therapy with cetuximab after FOLFIRI plus cetuximab for ras wild-type metastatic colorectal cancer: a phase 2 randomized clinical trial. JAMA Netw Open 6(9):e2333533. https://doi.org/10.1001/jamanetworkopen.2023.33533CrossRefPubMedPubMedCentral

Chen X, Qiu T, Zhu Y, Sun J, Li P, Wang B, Gu Y (2019) A single-arm, phase II study of apatinib in refractory metastatic colorectal cancer. Oncologist 24(7):883-e407. https://doi.org/10.1634/theoncologist.2019-0164CrossRefPubMedPubMedCentral

Chen H, Pan Y, Zhou Q, Liang C, Wong CC, Zhou Y, Yu J (2022a) METTL3 inhibits antitumor immunity by targeting m(6)A-BHLHE41-CXCL1/CXCR2 axis to promote colorectal cancer. Gastroenterology 163(4):891–907. https://doi.org/10.1053/j.gastro.2022.06.024CrossRefPubMed

Chen Z, Zhang X, Xing Z, Lv S, Huang L, Liu J, He Y (2022b) OLFM4 deficiency delays the progression of colitis to colorectal cancer by abrogating PMN-MDSCs recruitment. Oncogene 41(22):3131–3150. https://doi.org/10.1038/s41388-022-02324-8CrossRefPubMed

Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Guan Z (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10(1):25–34. https://doi.org/10.1016/s1470-2045(08)70285-7CrossRefPubMed

Chiu DK, Tse AP, Xu IM, Di Cui J, Lai RK, Li LL, Wong CC (2017) Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma. Nat Commun 8(1):517. https://doi.org/10.1038/s41467-017-00530-7CrossRefPubMedPubMedCentral

Denda T, Sakai D, Hamaguchi T, Sugimoto N, Ura T, Yamazaki K, Yoshino T (2019) Phase II trial of aflibercept with FOLFIRI as a second-line treatment for Japanese patients with metastatic colorectal cancer. Cancer Sci 110(3):1032–1043. https://doi.org/10.1111/cas.13943CrossRefPubMedPubMedCentral

Ducarouge B, Redavid A-R, Victoor C, Chira R, Fonseca A, Hervieu M, Bernet A (2023) Netrin-1 blockade inhibits tumor associated Myeloid-derived suppressor cells, cancer stemness and alleviates resistance to chemotherapy and immune checkpoint inhibitor. Cell Death Differ 30(10):2201–2212. https://doi.org/10.1038/s41418-023-01209-xCrossRefPubMed

Fakih M, Raghav KPS, Chang DZ, Larson T, Cohn AL, Huyck TK, Paulson AS (2023a) Regorafenib plus nivolumab in patients with mismatch repair-proficient/microsatellite stable metastatic colorectal cancer: a single-arm, open-label, multicentre phase 2 study. EClinicalMedicine 58:101917. https://doi.org/10.1016/j.eclinm.2023.101917CrossRefPubMedPubMedCentral

Fakih M, Sandhu J, Lim D, Li X, Li S, Wang C (2023b) Regorafenib, ipilimumab, and nivolumab for patients with microsatellite stable colorectal cancer and disease progression with prior chemotherapy: a phase 1 nonrandomized clinical trial. JAMA Oncol 9(5):627–634. https://doi.org/10.1001/jamaoncol.2022.7845CrossRefPubMedPubMedCentral

Friis S, Riis AH, Erichsen R, Baron JA, Sørensen HT (2015) Low-dose aspirin or nonsteroidal anti-inflammatory drug use and colorectal cancer risk. Ann Intern Med 163(5):347–355. https://doi.org/10.7326/M15-0039CrossRefPubMed

Gabrilovich DI (2017) Myeloid-derived suppressor cells. Cancer Immunol Res 5(1):3–8. https://doi.org/10.1158/2326-6066.Cir-16-0297CrossRefPubMedPubMedCentral

Galluzzi L, Humeau J, Buqué A, Zitvogel L, Kroemer G (2020) Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol 17(12):725–741. https://doi.org/10.1038/s41571-020-0413-zCrossRefPubMed

Garcia-Carbonero R, Rivera F, Maurel J, Ayoub JP, Moore MJ, Cervantes A, Tabernero J (2014) An open-label phase II study evaluating the safety and efficacy of ramucirumab combined with mFOLFOX-6 as first-line therapy for metastatic colorectal cancer. Oncologist 19(4):350–351. https://doi.org/10.1634/theoncologist.2014-0028CrossRefPubMedPubMedCentral

Grivennikov S, Karin E, Terzic J, Mucida D, Yu G, Vallabhapurapu S, Karin MJC (2009) IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15(2):103–113. https://doi.org/10.1016/j.ccr.2009.01.001CrossRefPubMedPubMedCentral

Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Laurent D (2013) Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381(9863):303–312. https://doi.org/10.1016/s0140-6736(12)61900-xCrossRefPubMed

Gürlevik E, Fleischmann-Mundt B, Brooks J, Demir I, Steiger K, Ribback S, Kühnel FJG (2016) Administration of gemcitabine after pancreatic tumor resection in mice induces an antitumor immune response mediated by natural killer. Cells 151(2):338-350.e337. https://doi.org/10.1053/j.gastro.2016.05.004CrossRef

Haag GM, Springfeld C, Grün B, Apostolidis L, Zschäbitz S, Dietrich M, Jaeger D (2022) Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer - The PICCASSO phase I trial. Eur J Cancer 167:112–122. https://doi.org/10.1016/j.ejca.2022.03.017CrossRefPubMed

Hailemichael Y, Johnson DH, Abdel-Wahab N, Foo WC, Bentebibel S-E, Daher M, Diab A (2022) Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity. Cancer Cell 40(5):509-523.e506. https://doi.org/10.1016/j.ccell.2022.04.004CrossRefPubMedPubMedCentral

Hashimoto A, Fukumoto T, Zhang R, Gabrilovich D (2020) Selective targeting of different populations of myeloid-derived suppressor cells by histone deacetylase inhibitors. Cancer Immunol Immunother 69(9):1929–1936. https://doi.org/10.1007/s00262-020-02588-7CrossRefPubMedPubMedCentral

Hayter CR, Huff-Winters C, Paszat L, Youssef YM, Shelley WE, Schulze K (2000) A prospective trial of short-course radiotherapy plus chemotherapy for palliation of dysphagia from advanced esophageal cancer. Radiother Oncol 56(3):329–333. https://doi.org/10.1016/s0167-8140(00)00225-5CrossRefPubMed

Hegde S, Leader AM, Merad M (2021) MDSC: Markers, development, states, and unaddressed complexity. Immunity 54(5):875–884. https://doi.org/10.1016/j.immuni.2021.04.004CrossRefPubMedPubMedCentral

Heinrich MC, Jones RL, George S, Gelderblom H, Schöffski P, von Mehren M, Bauer S (2024) Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial. Nat Med 30(2):498–506. https://doi.org/10.1038/s41591-023-02734-5CrossRefPubMedPubMedCentral

Hengesbach LM, Hoag KA (2004) Physiological concentrations of retinoic acid favor myeloid dendritic cell development over granulocyte development in cultures of bone marrow cells from mice. J Nutr 134(10):2653–2659. https://doi.org/10.1093/jn/134.10.2653CrossRefPubMed

Hsu N-Y, Nayar S, Gettler K, Talware S, Giri M, Alter I, Cho JH (2022) NOX1 is essential for TNFα-induced intestinal epithelial ROS secretion and inhibits M cell signatures. Gut 72(4):654–662. https://doi.org/10.1136/gutjnl-2021-326305CrossRefPubMed

Hu S, Fang Y, Chen X, Cheng T, Zhao M, Du M, Chen ZJ (2021) cGAS restricts colon cancer development by protecting intestinal barrier integrity. Proc Natl Acad Sci 118(23):e2105747118. https://doi.org/10.1073/pnas.2105747118CrossRefPubMedPubMedCentral

Huang T, Cheng X, Chahoud J, Sarhan A, Tamboli P, Rao P, Lu X (2020) Effective combinatorial immunotherapy for penile squamous cell carcinoma. Nat Commun. https://doi.org/10.1038/s41467-020-15980-9CrossRefPubMedPubMedCentral

Ibrahim ML, Klement JD, Lu C, Redd PS, Xiao W, Yang D, Liu K (2018) Myeloid-derived suppressor cells produce IL-10 to elicit DNMT3b-dependent IRF8 silencing to promote colitis-associated colon tumorigenesis. Cell Rep 25(11):3036-3046.e3036. https://doi.org/10.1016/j.celrep.2018.11.050CrossRefPubMedPubMedCentral

Jiang TY, Cui XW, Zeng TM, Pan YF, Lin YK, Feng XF, Wang HY (2023) PTEN deficiency facilitates gemcitabine efficacy in cancer by modulating the phosphorylation of PP2Ac and DCK. Sci Transl Med 15(704):eadd7464. https://doi.org/10.1126/scitranslmed.add7464CrossRefPubMed

Johnson M, Dudek AZ, Sukari A, Call J, Kunk PR, Lewis K, Goldman JW (2022) ARRY-382 in Combination with pembrolizumab in patients with advanced solid tumors: results from a phase 1b/2 Study. Clin Cancer Res 28(12):2517–2526. https://doi.org/10.1158/1078-0432.Ccr-21-3009CrossRefPubMedPubMedCentral

Kang YK, Ryu MH, Park SH, Kim JG, Kim JW, Cho SH, Oh SC (2018) Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy. Ann Oncol 29(5):1220–1226. https://doi.org/10.1093/annonc/mdy055CrossRefPubMed

Karpisheh V, Nikkhoo A, Hojjat-Farsangi M, Namdar A, Azizi G, Ghalamfarsa G, Jadidi-Niaragh F (2019) Prostaglandin E2 as a potent therapeutic target for treatment of colon cancer. Prostaglandins Other Lipid Mediat 144:106338. https://doi.org/10.1016/j.prostaglandins.2019.106338CrossRefPubMed

Ke Z, Wang C, Wu T, Wang W, Yang Y, Dai YJC (2020) PAR2 deficiency enhances myeloid cell-mediated immunosuppression and promotes colitis-associated tumorigenesis. Cancer Lett 469:437–446. https://doi.org/10.1016/j.canlet.2019.11.015CrossRefPubMed

Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Vogel A (2023) Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 401(10391):1853–1865. https://doi.org/10.1016/s0140-6736(23)00727-4CrossRefPubMed

Kim W, Chu TH, Nienhüser H, Jiang Z, Del Portillo A, Remotti HE, Wang TC (2021) PD-1 signaling promotes tumor-infiltrating myeloid-derived suppressor cells and gastric tumorigenesis in mice. Gastroenterology 160(3):781–796. https://doi.org/10.1053/j.gastro.2020.10.036CrossRefPubMed

Kim R, Hashimoto A, Markosyan N, Tyurin V, Tyurina Y, Kar G, Gabrilovich DJN (2022) Ferroptosis of tumour neutrophils causes immune suppression in cancer. Nature 612(7939):338–346. https://doi.org/10.1038/s41586-022-05443-0CrossRefPubMedPubMedCentral

Kopetz S, Desai J, Chan E, Hecht JR, O’Dwyer PJ, Maru D, Saltz L (2015) Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer. J Clin Oncol 33(34):4032–4038. https://doi.org/10.1200/jco.2015.63.2497CrossRefPubMedPubMedCentral

Krishnamoorthy M, Gerhardt L, Maleki Vareki S (2021) Immunosuppressive effects of myeloid-derived suppressor cells in cancer and immunotherapy. Cells 10(5):1170. https://doi.org/10.3390/cells10051170CrossRefPubMedPubMedCentral

Laubach JP, Liu C-J, Raje NS, Yee AJ, Armand P, Schlossman RL, Ghobrial IM (2019) A phase I/II study of evofosfamide, a hypoxia-activated prodrug with or without bortezomib in subjects with relapsed/refractory multiple myeloma. Clin Cancer Res 25(2):478–486. https://doi.org/10.1158/1078-0432.CCR-18-1325CrossRefPubMed

Laws M, Walker E, Cozzi F, Ampie L, Jung M, Burton E, Brown DJF (2023) Glioblastoma may evade immune surveillance through primary cilia-dependent signaling in an IL-6 dependent manner. Front Oncol 13:1279923. https://doi.org/10.3389/fonc.2023.1279923CrossRefPubMedPubMedCentral

Lee K, Kim HM (2011) A novel approach to cancer therapy using PX-478 as a HIF-1α inhibitor. Arch Pharmacal Res 34(10):1583–1585. https://doi.org/10.1007/s12272-011-1021-3CrossRef

Li T, Li X, Zamani A, Wang W, Lee C, Li M, Chen YJN (2020) c-Rel Is a myeloid checkpoint for cancer immunotherapy. Nat Cancer 1(5):507–517. https://doi.org/10.1038/s43018-020-0061-3CrossRefPubMedPubMedCentral

Liao W, Overman MJ, Boutin AT, Shang X, Zhao D, Dey P, DePinho RA (2019) KRAS-IRF2 axis drives immune suppression and immune therapy resistance in colorectal cancer. Cancer Cell 35(4):559-572.e557. https://doi.org/10.1016/j.ccell.2019.02.008CrossRefPubMedPubMedCentral

Limagne E, Euvrard R, Thibaudin M, Rébé C, Derangère V, Chevriaux A, Ghiringhelli F (2016a) Accumulation of MDSC and Th17 cells in patients with metastatic colorectal cancer predicts the efficacy of a FOLFOX-bevacizumab drug treatment regimen. Cancer Res 76(18):5241–5252. https://doi.org/10.1158/0008-5472.Can-15-3164CrossRefPubMed

Limagne E, Euvrard R, Thibaudin M, Rébé C, Derangère V, Chevriaux A, Ghiringhelli F (2016b) Accumulation of MDSC and Th17 cells in patients with metastatic colorectal cancer predicts the efficacy of a FOLFOX–bevacizumab drug treatment regimen. Can Res 76(18):5241–5252. https://doi.org/10.1158/0008-5472.CAN-15-3164CrossRef

Liu Z, Xie Y, Xiong Y, Liu S, Qiu C, Zhu Z, Wang X (2020) TLR 7/8 agonist reverses oxaliplatin resistance in colorectal cancer via directing the myeloid-derived suppressor cells to tumoricidal M1-macrophages. Cancer Lett 469:173–185. https://doi.org/10.1016/j.canlet.2019.10.020CrossRefPubMed

Liu H, Lou J, Liu Y, Liu Z, Xie J, Sun J, Han W (2022) Intestinal epithelial cell autophagy deficiency suppresses inflammation-associated colon tumorigenesis. Molecular Thera Py—Nucleic Acids 28:35–46. https://doi.org/10.1016/j.omtn.2022.02.012CrossRef

Liu H, Deng R, Zhu C-W, Han H-K, Zong G-F, Ren L, Lu Y (2023a) Rosmarinic acid in combination with ginsenoside Rg1 suppresses colon cancer metastasis via co-inhition of COX-2 and PD1/PD-L1 signaling axis. Acta Pharmacol Sin 45(1):193–208. https://doi.org/10.1038/s41401-023-01158-8CrossRefPubMed

Liu X, Tang R, Xu J, Tan Z, Liang C, Meng Q, Shi S (2023b) CRIP1 fosters MDSC trafficking and resets tumour microenvironment via facilitating NF-κB/p65 nuclear translocation in pancreatic ductal adenocarcinoma. Gut 72(12):2329–2343. https://doi.org/10.1136/gutjnl-2022-329349CrossRefPubMed

Luke JJ, Fakih M, Schneider C, Chiorean EG, Bendell J, Kristeleit R, Naing A (2023) Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors. Br J Cancer 128(12):2227–2235. https://doi.org/10.1038/s41416-023-02267-1CrossRefPubMedPubMedCentral

Ma Z, Zhen Y, Hu C, Yi HJF (2020) Myeloid-derived suppressor cell-derived arginase-1 oppositely modulates IL-17A and IL-17F Through the ESR/STAT3 pathway during colitis in mice. Front Immunol 11:687. https://doi.org/10.3389/fimmu.2020.00687CrossRefPubMedPubMedCentral

Mabrouk AA, El-Mezayen NS, Tadros MI, El-Gazayerly ON, El-Refaie WM (2023) Novel mucoadhesive celecoxib-loaded cubosomal sponges: anticancer potential and regulation of myeloid-derived suppressor cells in oral squamous cell carcinoma. Eur J Pharm Biopharm 182:62–80. https://doi.org/10.1016/j.ejpb.2022.12.003CrossRefPubMed

Mao Y, Eissler N, Blanc KL, Johnsen JI, Kogner P, Kiessling R (2016) Targeting suppressive myeloid cells potentiates checkpoint inhibitors to control spontaneous neuroblastoma. Clin Cancer Res 22(15):3849–3859. https://doi.org/10.1158/1078-0432.CCR-15-1912CrossRefPubMed

Mehta AR, Armstrong AJ (2016) Tasquinimod in the treatment of castrate-resistant prostate cancer - current status and future prospects. Ther Adv Urol 8(1):9–18. https://doi.org/10.1177/1756287215603558CrossRefPubMedPubMedCentral

Meric-Bernstam F, Hurwitz H, Raghav KPS, McWilliams RR, Fakih M, VanderWalde A, Hainsworth J (2019) Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol 20(4):518–530. https://doi.org/10.1016/s1470-2045(18)30904-5CrossRefPubMedPubMedCentral

Michaelis KA, Norgard MA, Zhu X, Levasseur PR, Sivagnanam S, Liudahl SM, Marks DL (2019) The TLR7/8 agonist R848 remodels tumor and host responses to promote survival in pancreatic cancer. Nat Commun 10(1):4682. https://doi.org/10.1038/s41467-019-12657-wCrossRefPubMedPubMedCentral

Minematsu H, Afify S, Sugihara Y, Hassan G, Zahra M, Seno A, Seno M (2022) Cancer stem cells induced by chronic stimulation with prostaglandin E2 exhibited constitutively activated PI3K axis. Sci Rep 12(1):15628. https://doi.org/10.1038/s41598-022-19265-7CrossRefPubMedPubMedCentral

Mo W, Liu S, Zhao X, Wei F, Li Y, Sheng X, Guo H (2023) ROS Scavenging Nanozyme Modulates Immunosuppression for Sensitized Cancer Immunotherapy. Adv Healthc Mater 12(21):e2300191. https://doi.org/10.1002/adhm.202300191CrossRefPubMed

Morano F, Corallo S, Lonardi S, Raimondi A, Cremolini C, Rimassa L, Pietrantonio F (2019) Negative hyperselection of patients with ras and braf wild-type metastatic colorectal cancer who received panitumumab-based maintenance therapy. J Clin Oncol 37(33):3099–3110. https://doi.org/10.1200/jco.19.01254CrossRefPubMedPubMedCentral

Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag C, Laversanne M, Bray FJG (2023) Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut 72(2):338–344. https://doi.org/10.1136/gutjnl-2022-327736CrossRefPubMed

Nenci A, Becker C, Wullaert A, Gareus R, van Loo G, Danese S, Pasparakis M (2007) Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446(7135):557–561. https://doi.org/10.1038/nature05698CrossRefPubMed

Nywening TM, Wang-Gillam A, Sanford DE, Belt BA, Panni RZ, Cusworth BM, Linehan DC (2016) Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol 17(5):651–662. https://doi.org/10.1016/s1470-2045(16)00078-4CrossRefPubMedPubMedCentral

Olson DJ, Luke JJ (2023) Myeloid maturity: ATRA to enhance anti-PD-1? Clin Cancer Res 29(7):1167–1169. https://doi.org/10.1158/1078-0432.Ccr-22-3652CrossRefPubMedPubMedCentral

Omahony C, Clooney A, Clarke S, Aguilera M, Gavin A, Simnica D, Melgar S (2023) Dietary-induced bacterial metabolites reduce inflammation and inflammation associated cancer via vitamin D pathway. Int J Mol Sci 24(3):1864. https://doi.org/10.3390/ijms24031864CrossRefPubMed

Qin S, Li J, Bai Y, Deng Y, Yang L, Xu RH, Shen L (2021) Quality-adjusted survival in patients with metastatic colorectal cancer treated with fruquintinib in the FRESCO trial. Future Oncol 17(15):1923–1931. https://doi.org/10.2217/fon-2020-1215CrossRefPubMed

Qin G, Liu S, Liu J, Hu H, Yang L, Zhao Q (2023) Overcoming resistance to immunotherapy by targeting GPR84 in myeloid-derived suppressor cells. Signal Transduct Target Therap 8(1):164. https://doi.org/10.1038/s41392-023-01388-6CrossRef

Reilley MJ, McCoon P, Cook C, Lyne P, Kurzrock R, Kim Y, Hong DS (2018) STAT3 antisense oligonucleotide AZD9150 in a subset of patients with heavily pretreated lymphoma: results of a phase 1b trial. J Immunother Cancer 6(1):119. https://doi.org/10.1186/s40425-018-0436-5CrossRefPubMedPubMedCentral

Ruiz-Saenz A, Atreya CE, Wang C, Pan B, Dreyer CA, Brunen D, Coppé J-P (2023) A reversible SRC-relayed COX2 inflammatory program drives resistance to BRAF and EGFR inhibition in BRAFV600E colorectal tumors. Nature Cancer 4(2):240–256. https://doi.org/10.1038/s43018-022-00508-5CrossRefPubMedPubMedCentral

Saeed A, Park R, Pathak H, Al-Bzour AN, Dai J, Phadnis M, Saeed A (2024) Clinical and biomarker results from a phase II trial of combined cabozantinib and durvalumab in patients with chemotherapy-refractory colorectal cancer (CRC): CAMILLA CRC cohort. Nat Commun 15(1):1533. https://doi.org/10.1038/s41467-024-45960-2CrossRefPubMedPubMedCentral

Sarkar O, Donninger H, Al Rayyan N, Chew L, Stamp B, Zhang X, Yaddanapudi K (2023) Monocytic MDSCs exhibit superior immune suppression via adenosine and depletion of adenosine improves efficacy of immunotherapy. Sci Adv 9(26):3736. https://doi.org/10.1126/sciadv.adg3736CrossRef

Shojaei F, Wu X, Malik AK, Zhong C, Baldwin ME, Schanz S, Ferrara N (2007) Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 25(8):911–920. https://doi.org/10.1038/nbt1323CrossRefPubMed

Siegel R, Wagle N, Cercek A, Smith R, Jemal A (2023) Colorectal cancer statistics, 2023. CA Cancer J Clin 73(3):233–254. https://doi.org/10.3322/caac.21772CrossRefPubMed

Song Q, Zhao H, Zheng C, Wang K, Gao H, Feng Q, Wang L (2021) A bioinspired versatile spore coat nanomaterial for oral probiotics delivery. Adv Func Mater 31(41):2104994. https://doi.org/10.1002/adfm.202104994CrossRef

Spaander M, Zauber A, Syngal S, Blaser M, Sung J, You Y, Kuipers EJ (2023) Young-onset colorectal cancer. Nat Rev Dis Primers 9(1):21. https://doi.org/10.1038/s41572-023-00432-7CrossRefPubMedPubMedCentral

Strickler JH, Cercek A, Siena S, André T, Ng K, Van Cutsem E, Shao S (2023) Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol 24(5):496–508. https://doi.org/10.1016/S1470-2045(23)00150-XCrossRefPubMed

Thiele Orberg E, Fan H, Tam AJ, Dejea CM, Destefano Shields CE, Wu S, Housseau F (2017) The myeloid immune signature of enterotoxigenic Bacteroides fragilis-induced murine colon tumorigenesis. Mucosal Immunol 10(2):421–433. https://doi.org/10.1038/mi.2016.53CrossRefPubMed

Tobin RP, Cogswell DT, Cates VM, Davis DM, Borgers JSW, Van Gulick RJ, McCarter MD (2023) Targeting MDSC differentiation using ATRA: a phase I/II clinical trial combining pembrolizumab and all-trans retinoic acid for metastatic melanoma. Clin Cancer Res 29(7):1209–1219. https://doi.org/10.1158/1078-0432.Ccr-22-2495CrossRefPubMedPubMedCentral

Tsien CI, Pugh SL, Dicker AP, Raizer JJ, Matuszak MM, Lallana EC, Mehta MP (2023) NRG Oncology/RTOG1205: a randomized phase ii trial of concurrent bevacizumab and reirradiation versus bevacizumab alone as treatment for recurrent glioblastoma. J Clin Oncol 41(6):1285–1295. https://doi.org/10.1200/jco.22.00164CrossRefPubMed

Tsukamoto H, Nishikata R, Senju S, Nishimura Y (2013) Myeloid-derived suppressor cells attenuate th1 development through il-6 production to promote tumor progression. Cancer Immunol Res 1(1):64–76. https://doi.org/10.1158/2326-6066.CIR-13-0030CrossRefPubMed

Tu S, Bhagat G, Cui G, Takaishi S, Kurt-Jones EA, Rickman B, Wang TC (2008) Overexpression of interleukin-1β induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 14(5):408–419. https://doi.org/10.1016/j.ccr.2008.10.011CrossRefPubMedPubMedCentral

Vallilas C, Sarantis P, Kyriazoglou A, Koustas E, Theocharis S, Papavassiliou AG, Karamouzis MV (2021) Gastrointestinal Stromal Tumors (GISTs): Novel Therapeutic Strategies with Immunotherapy and Small Molecules. Int J Mol Sci 22(2):493. https://doi.org/10.3390/ijms22020493CrossRefPubMedPubMedCentral

Wan D, Yang Y, Liu Y, Cun X, Li M, Xu S, He Q (2020) Sequential depletion of myeloid-derived suppressor cells and tumor cells with a dual-pH-sensitive conjugated micelle system for cancer chemoimmunotherapy. J Control Release 317:43–56. https://doi.org/10.1016/j.jconrel.2019.11.011CrossRefPubMed

Wang Y, Ding Y, Deng Y, Zheng Y, Wang S (2020) Role of myeloid-derived suppressor cells in the promotion and immunotherapy of colitis-associated cancer. J Immunother Cancer 8(2):e000609. https://doi.org/10.1136/jitc-2020-000609CrossRefPubMedPubMedCentral

Wang C, Zheng X, Zhang J, Jiang X, Wang J, Li Y, Luo M (2023a) CD300ld on neutrophils is required for tumour-driven immune suppression. Nature 621(7980):830–839. https://doi.org/10.1038/s41586-023-06511-9CrossRefPubMed

Wang L, Mou H, Hou X, Liao Q (2023b) Case report: a case of complete clinical response in a patient experiencing high microsatellite instability unresectable colon cancer being treated with a PD-L1 inhibitor after interstitial pneumonia. Front Oncol 13:1126769. https://doi.org/10.3389/fonc.2023.1126769CrossRefPubMedPubMedCentral

Wang Q, Long G, Luo H, Zhu X, Han Y, Shang Y (2023c) S100A8/A9: An emerging player in sepsis and sepsis-induced organ injury. Biomed Pharmacother 168:115674. https://doi.org/10.1016/j.biopha.2023.115674CrossRefPubMed

Wang X, Zhang D, Yang Y, Li X, Li H, Zhang X, Ma XJ (2023d) viaSuppression of microRNA-222-3p ameliorates ulcerative colitis and colitis-associated colorectal cancer to protect against oxidative stress targeting BRG1 to activate Nrf2/HO-1 signaling pathway. Front Immunol 14:1089809. https://doi.org/10.3389/fimmu.2023.1089809CrossRefPubMedPubMedCentral

Wang Y, Liu H, Zhang Z, Bian D, Shao K, Wang S, Ding YJJ (2023e) G-MDSC-derived exosomes mediate the differentiation of M-MDSC into M2 macrophages promoting colitistocancer transition. J Immunother Cancer 11(6):e006166. https://doi.org/10.1136/jitc-2022-006166CrossRefPubMedPubMedCentral

Webster-Clark M, Keil AP, Robert N, Frytak JR, Boyd M, Stürmer T, Lund JL (2022) Comparing trial and real-world adjuvant oxaliplatin delivery in patients with stage III colon cancer using a longitudinal cumulative dose. JAMA Oncol 8(12):1821–1824. https://doi.org/10.1001/jamaoncol.2022.4445CrossRefPubMedPubMedCentral

Weed DT, Vella JL, Reis IM, De la Fuente AC, Gomez C, Sargi Z, Serafini P (2015) Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res 21(1):39–48. https://doi.org/10.1158/1078-0432.Ccr-14-1711CrossRefPubMed

Wu L, Xu Y, Zhao H, Zhou Y, Chen Y, Yang S, Li YJT (2022a) FcγRIIB potentiates differentiation of myeloid-derived suppressor cells to mediate tumor immunoescape. Theranostics 12(2):842–858. https://doi.org/10.7150/thno.66575CrossRefPubMedPubMedCentral

Wu Y, Yi M, Niu M, Mei Q, Wu K (2022b) Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy. Mol Cancer 21(1):184. https://doi.org/10.1186/s12943-022-01657-yCrossRefPubMedPubMedCentral

Xie Z, Ikegami T, Ago Y, Okada N, Tachibana M (2020) Valproic acid attenuates CCR2-dependent tumor infiltration of monocytic myeloid-derived suppressor cells, limiting tumor progression. OncoImmunology 9(1):1734268. https://doi.org/10.1080/2162402X.2020.1734268CrossRefPubMedPubMedCentral

Xu RH, Shen L, Wang KM, Wu G, Shi CM, Ding KF, Yu H (2017) Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial. Chin J Cancer 36(1):97. https://doi.org/10.1186/s40880-017-0263-yCrossRefPubMedPubMedCentral

Xun J, Zhou S, Lv Z, Wang B, Luo H, Zhang L, Zhang Q (2023) Dioscin modulates macrophages polarization and MDSCs differentiation to inhibit tumorigenesis of colitis-associated colorectal cancer. Int Immunopharmacol 117:109839. https://doi.org/10.1016/j.intimp.2023.109839CrossRefPubMed

Yang L, Huang J, Ren X, Gorska AE, Chytil A, Aakre M, Moses HL (2008) Abrogation of TGFβ signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. Cancer Cell 13(1):23–35. https://doi.org/10.1016/j.ccr.2007.12.004CrossRefPubMedPubMedCentral

Yang Y, Gharaibeh RZ, Newsome RC, Jobin C (2020) Amending microbiota by targeting intestinal inflammation with TNF blockade attenuates development of colorectal cancer. Nature Cancer 1(7):723–734. https://doi.org/10.1038/s43018-020-0078-7CrossRefPubMedPubMedCentral

Yang X, Li G, Lou P, Zhang M, Yao K, Xiao J, Lv C (2024) Excessive nucleic acid R-loops induce mitochondria-dependent epithelial cell necroptosis and drive spontaneous intestinal inflammation. Proc Natl Acad Sci U S A 121(1):e2307395120. https://doi.org/10.1073/pnas.2307395120CrossRefPubMed

Yap TA, Vieito M, Baldini C, Sepúlveda-Sánchez JM, Kondo S, Simonelli M, Melisi D (2021) First-in-human phase I study of a next-generation, oral, TGFβ receptor 1 inhibitor, LY3200882, in patients with advanced cancer. Clin Cancer Res 27(24):6666–6676. https://doi.org/10.1158/1078-0432.Ccr-21-1504CrossRefPubMedPubMedCentral

Ye Y, Wang X, Jeschke U, von Schönfeldt V (2020) COX-2-PGE(2)-EPs in gynecological cancers. Arch Gynecol Obstet 301(6):1365–1375. https://doi.org/10.1007/s00404-020-05559-6CrossRefPubMedPubMedCentral

Youn JI, Nagaraj S, Collazo M, Gabrilovich DI (2008) Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol 181(8):5791–5802. https://doi.org/10.4049/jimmunol.181.8.5791CrossRefPubMed

Yvellez OV, Rai V, Sossenheimer PH, Hart J, Turner JR, Weber C, Rubin DT (2021) Cumulative histologic inflammation predicts colorectal neoplasia in ulcerative colitis: a validation study. Inflamm Bowel Dis 27(2):203–206. https://doi.org/10.1093/ibd/izaa047CrossRefPubMed

Zhang Q, Ma C, Duan Y, Heinrich B, Rosato U, Diggs LP, Greten TF (2020) Gut microbiome directs hepatocytes to recruit MDSCS and promote cholangiocarcinoma. Cancer Discov 11(5):1248–1267. https://doi.org/10.1158/2159-8290.CD-20-0304CrossRefPubMedPubMedCentral

Zhang J, Simpson CM, Berner J, Chong HB, Fang J, Ordulu Z, Bar-Peled L (2023) Systematic identification of anticancer drug targets reveals a nucleus-to-mitochondria ROS-sensing pathway. Cell 186(11):2361-2379.e2325. https://doi.org/10.1016/j.cell.2023.04.026CrossRefPubMed

Zhang K, Zakeri A, Alban T, Dong J, Ta HM, Zalavadia AH, Wang LL (2024) VISTA promotes the metabolism and differentiation of myeloid-derived suppressor cells by STAT3 and polyamine-dependent mechanisms. Cell Rep 43(1):113661. https://doi.org/10.1016/j.celrep.2023.113661CrossRefPubMedPubMedCentral

Zhou AP, Bai Y, Song Y, Luo H, Ren XB, Wang X, Ma J (2019) Anlotinib versus sunitinib as first-line treatment for metastatic renal cell carcinoma: a randomized phase II clinical trial. Oncologist 24(8):e702–e708. https://doi.org/10.1634/theoncologist.2018-0839CrossRefPubMedPubMedCentral

Zhou Q, Peng Y, Ji F, Chen H, Kang W, Chan LS, Wong CC (2023) Targeting of SLC25A22 boosts the immunotherapeutic response in KRAS-mutant colorectal cancer. Nat Commun 14(1):4677. https://doi.org/10.1038/s41467-023-39571-6CrossRefPubMedPubMedCentral

Zhu W, Chu H, Zhang Y, Luo T, Yu H, Zhu H, Yang WJC (2023) Fructose-1,6-bisphosphatase 1 dephosphorylates IκBα and suppresses colorectal tumorigenesis. Cell Res 33(3):245–257. https://doi.org/10.1038/s41422-022-00773-0CrossRefPubMedPubMedCentral

Title: Role played by MDSC in colitis-associated colorectal cancer and potential therapeutic strategies
Authors: Kang Wang
Yun Wang
Kai Yin
Publication date: 01-05-2024
Publisher: Springer Berlin Heidelberg
Keywords: Colorectal Cancer
Colorectal Cancer
Published in: Journal of Cancer Research and Clinical Oncology / Issue 5/2024
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-024-05755-w

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