Skip to main content
Top

25-04-2024 | SCLC | RESEARCH ARTICLE

Peripheral NK cells identified as the predictor of response in extensive-stage small cell lung cancer patients treated with first-line immunotherapy plus chemotherapy

Authors: Yanan Cui, Yanping Chen, Peiyan Zhao, Shuang Li, Ying Cheng, Xiubao Ren

Published in: Clinical and Translational Oncology

Login to get access

Abstract

Purpose

Although immunotherapy improves outcomes in extensive-stage small-cell lung cancer (ES-SCLC), the search for biomarkers predicting treatment success is crucial. Natural killer (NK) cells are potential indicators in various cancers, however, their precise role in ES-SCLC prognosis remains unclear.

Methods

In this retrospective study, 33 patients with ES-SCLC treated with first-line immuno-chemotherapy were enrolled. The peripheral NK cell percentage and its longitudinal dynamics were analyzed using flow cytometry. Progression-free survival (PFS) and overall survival (OS) were calculated as hazard ratio (HR) and compared statistically.

Results

The median PFS was better in the group with normal baseline NK cell levels than the low group (7.0 vs. 4.6 months; HR = 0.17; 95% CI 0.07–0.41; P < 0.0001), but there was no association with OS (14.9 vs. 10.3 months; HR = 0.55; 95% CI 0.23–1.31; P = 0.171). Furthermore, the NK cell% for 95.0% of patients increased after immunochemotherapy in the clinical response group (P = 0.0047), which led to a better median PFS (6.3 vs. 2.1 months; HR = 0.23; 95% CI 0.05–0.98; P < 0.0001) and OS (14.9 vs. 5.9 months; HR = 0.20; 95% CI 0.04–1.02; P < 0.0001). Similar trends were observed with NK cell% changes up to disease progression, improving PFS (6.5 vs. 4.3; HR = 0.41; 95% CI 0.12–0.92; P = 0.0049) and OS (17.4 vs. 9.7; HR = 0.42; 95% CI 0.17–1.02; P < 0.0001).

Conclusion

In patients with ES-SCLC, the percentage and changes in peripheral NK cells can predict the response to combined immunotherapy and chemotherapy.
Literature
1.
go back to reference Megyesfalvi Z, Gay CM, Popper H, Pirker R, Ostoros G, Heeke S, et al. Clinical insights into small cell lung cancer: tumor heterogeneity, diagnosis, therapy, and future directions. CA Cancer J Clin. 2023;73:620–52.CrossRefPubMed Megyesfalvi Z, Gay CM, Popper H, Pirker R, Ostoros G, Heeke S, et al. Clinical insights into small cell lung cancer: tumor heterogeneity, diagnosis, therapy, and future directions. CA Cancer J Clin. 2023;73:620–52.CrossRefPubMed
4.
go back to reference Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379:2220–9.CrossRefPubMed Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379:2220–9.CrossRefPubMed
5.
go back to reference Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394:1929–39.CrossRefPubMed Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394:1929–39.CrossRefPubMed
6.
go back to reference Wang J, Zhou C, Yao W, Wang Q, Min X, Chenet G, et al. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23:739–47.CrossRefPubMed Wang J, Zhou C, Yao W, Wang Q, Min X, Chenet G, et al. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23:739–47.CrossRefPubMed
7.
go back to reference Cheng Y, Han L, Wu L, Chen J, Sun HBS, G W, et al. Effect of first-line serplulimab vs placebo added to chemotherapy on survival in patients with extensive-stage small cell lung cancer the ASTRUM-005 randomized clinical trial. JAMA. 2022;328:1223–32.CrossRefPubMedPubMedCentral Cheng Y, Han L, Wu L, Chen J, Sun HBS, G W, et al. Effect of first-line serplulimab vs placebo added to chemotherapy on survival in patients with extensive-stage small cell lung cancer the ASTRUM-005 randomized clinical trial. JAMA. 2022;328:1223–32.CrossRefPubMedPubMedCentral
8.
go back to reference Remon J, Aldea M, Besse B, Planchard D, Reck M, Giaccone G, et al. Small cell lung cancer: a slightly less orphan disease after immunotherapy. Ann Oncol. 2021;32:698–709.CrossRefPubMed Remon J, Aldea M, Besse B, Planchard D, Reck M, Giaccone G, et al. Small cell lung cancer: a slightly less orphan disease after immunotherapy. Ann Oncol. 2021;32:698–709.CrossRefPubMed
9.
go back to reference Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, et al. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2021;18:345–62.CrossRefPubMed Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, et al. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2021;18:345–62.CrossRefPubMed
10.
go back to reference Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, et al. Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133). J Clin Oncol. 2021;39:619–30.CrossRefPubMedPubMedCentral Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, et al. Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133). J Clin Oncol. 2021;39:619–30.CrossRefPubMedPubMedCentral
11.
go back to reference Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021;22:51–65.CrossRefPubMed Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021;22:51–65.CrossRefPubMed
12.
go back to reference Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, 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;21:1353–65.CrossRefPubMed Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, 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;21:1353–65.CrossRefPubMed
13.
go back to reference Hamilton G, Rath B. Immunotherapy for small cell lung cancer: mechanisms of resistance. Expert Opin Biol Ther. 2019;19:423–32.CrossRefPubMed Hamilton G, Rath B. Immunotherapy for small cell lung cancer: mechanisms of resistance. Expert Opin Biol Ther. 2019;19:423–32.CrossRefPubMed
14.
go back to reference Rudin CM, Balli D, Lai WV, Richards AL, Nguyen E, Egger JV, et al. Clinical benefit from immunotherapy in patients with SCLC is associated with tumor capacity for antigen presentation. J Thorac Oncol. 2023;18:1222–32.CrossRefPubMed Rudin CM, Balli D, Lai WV, Richards AL, Nguyen E, Egger JV, et al. Clinical benefit from immunotherapy in patients with SCLC is associated with tumor capacity for antigen presentation. J Thorac Oncol. 2023;18:1222–32.CrossRefPubMed
15.
go back to reference Best SA, Hess JB, Souza-Fonseca-Guimaraes F, Cursons J, Kersbergen A, Donget X, et al. Harnessing natural killer immunity in metastatic SCLC. J Thorac Oncol. 2020;15:1507–21.CrossRefPubMed Best SA, Hess JB, Souza-Fonseca-Guimaraes F, Cursons J, Kersbergen A, Donget X, et al. Harnessing natural killer immunity in metastatic SCLC. J Thorac Oncol. 2020;15:1507–21.CrossRefPubMed
16.
go back to reference Shapiro, HM. Practical flow cytometry: shapiro/flow cytometry 4e. 2005. Shapiro, HM. Practical flow cytometry: shapiro/flow cytometry 4e. 2005.
17.
go back to reference Bald T, Krummel MF, Smyth MJ, Barry KC. The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies. Nat Immunol. 2020;21:835–47.CrossRefPubMedPubMedCentral Bald T, Krummel MF, Smyth MJ, Barry KC. The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies. Nat Immunol. 2020;21:835–47.CrossRefPubMedPubMedCentral
19.
go back to reference Xie MZ, Tang YP, Hu BL, Li KZ, Li JL, Liang XQ. Percentage of natural killer (NK) cells in peripheral blood is associated with prognosis in patients with gastric cancer: a retrospective study from a single center. Med Sci Monit Int J Clin Exp. 2021;27:e927464. Xie MZ, Tang YP, Hu BL, Li KZ, Li JL, Liang XQ. Percentage of natural killer (NK) cells in peripheral blood is associated with prognosis in patients with gastric cancer: a retrospective study from a single center. Med Sci Monit Int J Clin Exp. 2021;27:e927464.
20.
go back to reference Tang YP, Xie MZ, Li KZ, Li JL, Cai ZM, Hu BL. Prognostic value of peripheral blood natural killer cells in colorectal cancer. BMC Gastroenterol. 2020;20:31.CrossRefPubMedPubMedCentral Tang YP, Xie MZ, Li KZ, Li JL, Cai ZM, Hu BL. Prognostic value of peripheral blood natural killer cells in colorectal cancer. BMC Gastroenterol. 2020;20:31.CrossRefPubMedPubMedCentral
21.
go back to reference Zhou J, Lin H-P, Xu X, Wang XH, Rong L, Zhang Y, et al. The predictive value of peripheral blood cells and lymphocyte subsets in oesophageal squamous cell cancer patients with neoadjuvant chemoradiotherapy. Front Immunol. 2022;13:1041126.CrossRefPubMedPubMedCentral Zhou J, Lin H-P, Xu X, Wang XH, Rong L, Zhang Y, et al. The predictive value of peripheral blood cells and lymphocyte subsets in oesophageal squamous cell cancer patients with neoadjuvant chemoradiotherapy. Front Immunol. 2022;13:1041126.CrossRefPubMedPubMedCentral
22.
go back to reference Tenuta M, Pandozzi C, Sciarra F, Campolo F, Gelibter AJ, Sirgiovanni G, et al. Circulating natural killer cells as prognostic value for non-small-cell lung cancer patients treated with immune checkpoint inhibitors: correlation with sarcopenia. Cancers (Basel). 2023;15:3592.CrossRefPubMed Tenuta M, Pandozzi C, Sciarra F, Campolo F, Gelibter AJ, Sirgiovanni G, et al. Circulating natural killer cells as prognostic value for non-small-cell lung cancer patients treated with immune checkpoint inhibitors: correlation with sarcopenia. Cancers (Basel). 2023;15:3592.CrossRefPubMed
23.
go back to reference Ma W, Wei S, Long S, Tian EC, McLaughlin B, Jaimes M, et al. Dynamic evaluation of blood immune cells predictive of response to immune checkpoint inhibitors in NSCLC by multicolor spectrum flow cytometry. Front Immunol. 2023;14:1206631.CrossRefPubMedPubMedCentral Ma W, Wei S, Long S, Tian EC, McLaughlin B, Jaimes M, et al. Dynamic evaluation of blood immune cells predictive of response to immune checkpoint inhibitors in NSCLC by multicolor spectrum flow cytometry. Front Immunol. 2023;14:1206631.CrossRefPubMedPubMedCentral
24.
go back to reference Pockley AG, Vaupel P, Multhoff G. NK cell-based therapeutics for lung cancer. Expert Opin Biol Ther. 2020;20:23–33.CrossRefPubMed Pockley AG, Vaupel P, Multhoff G. NK cell-based therapeutics for lung cancer. Expert Opin Biol Ther. 2020;20:23–33.CrossRefPubMed
25.
go back to reference Zhu M, Huang Y, Bender ME, Girard L, Kollipara R, Eglenen-Polat B, et al. Evasion of innate immunity contributes to small cell lung cancer progression and metastasis. Cancer Res. 2021;81:1813–26.CrossRefPubMedPubMedCentral Zhu M, Huang Y, Bender ME, Girard L, Kollipara R, Eglenen-Polat B, et al. Evasion of innate immunity contributes to small cell lung cancer progression and metastasis. Cancer Res. 2021;81:1813–26.CrossRefPubMedPubMedCentral
26.
go back to reference Gay CM, Stewart CA, Park EM, Diao L, Groves SM, Heeke S, et al. Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell. 2021;39:346–60.CrossRefPubMedPubMedCentral Gay CM, Stewart CA, Park EM, Diao L, Groves SM, Heeke S, et al. Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell. 2021;39:346–60.CrossRefPubMedPubMedCentral
27.
go back to reference Jeon EY, Choi DS, Choi S, Won JY, Jo Y, Kim HB, et al. Enhancing adoptive T-cell therapy with fucoidan-based IL-2 delivery microcapsules. Bioeng Transl Med. 2022;8: e10362.CrossRefPubMedPubMedCentral Jeon EY, Choi DS, Choi S, Won JY, Jo Y, Kim HB, et al. Enhancing adoptive T-cell therapy with fucoidan-based IL-2 delivery microcapsules. Bioeng Transl Med. 2022;8: e10362.CrossRefPubMedPubMedCentral
28.
go back to reference Burr ML, Sparbier CE, Chan KL, Chan YC, Kersbergen A, Lam EYN, et al. An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer. Cancer Cell. 2019;36:385–401.CrossRefPubMedPubMedCentral Burr ML, Sparbier CE, Chan KL, Chan YC, Kersbergen A, Lam EYN, et al. An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer. Cancer Cell. 2019;36:385–401.CrossRefPubMedPubMedCentral
29.
go back to reference Fousek K, Horn LA, Qin H, Dahut M, Iida M, Yacubovich D, et al. An interleukin-15 superagonist enables antitumor efficacy of natural killer cells against all molecular variants of SCLC. J Thorac Oncol. 2023;18:350–68.CrossRefPubMed Fousek K, Horn LA, Qin H, Dahut M, Iida M, Yacubovich D, et al. An interleukin-15 superagonist enables antitumor efficacy of natural killer cells against all molecular variants of SCLC. J Thorac Oncol. 2023;18:350–68.CrossRefPubMed
Metadata
Title
Peripheral NK cells identified as the predictor of response in extensive-stage small cell lung cancer patients treated with first-line immunotherapy plus chemotherapy
Authors
Yanan Cui
Yanping Chen
Peiyan Zhao
Shuang Li
Ying Cheng
Xiubao Ren
Publication date
25-04-2024
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-024-03479-4
Live Webinar | 01-10-2024 | 12:30 (CEST)

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

Live: Tuesday 1st October 2024, 12:30-14:00 (CEST)

In this live webinar, Professor Martin Dreyling and an esteemed, international panel of CAR-T experts will discuss the very 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, as presented at ASH 2023, EU CAR-T 2024, and EHA 2024. 

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