Immune Signatures of Solid Tumor Patients Treated With Immune Checkpoint Inhibitors: An Observational Study

Overview

Journal Thorac Cancer

Specialties Oncology
Pulmonary Medicine

Date 2024 Nov 25

PMID 39582218

Authors

Ling Chen

Hourui Tan

Ruixuan Geng

Yifan Li

Yingyi Wang

Taisheng Li

Affiliations

Soon will be listed here.

Abstract

Purpose: Our study aimed to comprehensively describe the features of peripheral blood multiple immune cell phenotypes in solid tumor patients during pretreatment and after immunotherapy, providing a more convenient approach for studying the prognosis of immunotherapy in different solid tumor patients.

Methods: We prospectively recruited patients with advanced solid tumors from Peking Union Medical College Hospital (PUMCH) between February 2023 and April 2024. Using multicolor flow cytometry, our study comprehensively observed and described the signatures of peripheral blood lymphocyte subsets including activation, proliferation, function, naïve memory, and T cell exhaustion immune cell subsets in this population of pretreatment and after immunotherapy.

Results: Our study enrolled 59 advanced solid tumor patients with immunotherapy and 59 healthy controls were matched by age and gender. The results demonstrated a marked upregulation in the expression of lymphocyte activation markers CD38 and HLA-DR, as well as exhaustion and proliferation markers PD-1 and Ki67, in solid tumor patients compared to healthy controls. After immune checkpoint blockade (ICB) treatment, mainly the expression of Ki67CD4+T and HLA-DRCD38CD4+T, was significantly upregulated compared to pretreatment levels (p = 0.017, p = 0.019, respectively). We further found that gynecological tumors with better prognoses had higher baseline activation levels of CD4+ T cells compared to other solid tumors with poorer prognoses.

Conclusion: Our study elucidated the characteristics of different lymphocyte subsets in the peripheral blood of solid tumor patients. Further research revealed changes in the phenotypes of different lymphocyte subsets after ICIs treatment, with the activated phenotype of CD4+ T cells playing a crucial role in the antitumor effect. This lays the groundwork for further exploration of prognostic biomarkers and predictive models for cancer patients with immunotherapy.

References

Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C . Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006; 313(5795):1960-4. DOI: 10.1126/science.1129139. View

Xiang Q, Liu Y, Xiao J, Ou L, Du J . Prognostic Value of Lymphocyte-to-Monocyte Ratio (LMR) in Patients With Prostate Cancer: A Systematic Review and Meta-Analysis. Am J Mens Health. 2024; 18(2):15579883241234747. PMC: 10958819. DOI: 10.1177/15579883241234747. View

Gorgulho J, Roderburg C, Beier F, Bokemeyer C, Brummendorf T, Loosen S . Soluble lymphocyte activation gene-3 (sLAG3) and CD4/CD8 ratio dynamics as predictive biomarkers in patients undergoing immune checkpoint blockade for solid malignancies. Br J Cancer. 2024; 130(6):1013-1022. PMC: 10951205. DOI: 10.1038/s41416-023-02558-7. View

Qin L, Jing X, Qiu Z, Cao W, Jiao Y, Routy J . Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults. Aging (Albany NY). 2016; 8(5):848-59. PMC: 4931839. DOI: 10.18632/aging.100894. View

Hiam-Galvez K, Allen B, Spitzer M . Systemic immunity in cancer. Nat Rev Cancer. 2021; 21(6):345-359. PMC: 8034277. DOI: 10.1038/s41568-021-00347-z. View

Zuazo M, Arasanz H, Fernandez-Hinojal G, Garcia-Granda M, Gato M, Bocanegra A . Functional systemic CD4 immunity is required for clinical responses to PD-L1/PD-1 blockade therapy. EMBO Mol Med. 2019; 11(7):e10293. PMC: 6609910. DOI: 10.15252/emmm.201910293. View

Jacquelot N, Roberti M, Enot D, Rusakiewicz S, Ternes N, Jegou S . Predictors of responses to immune checkpoint blockade in advanced melanoma. Nat Commun. 2017; 8(1):592. PMC: 5605517. DOI: 10.1038/s41467-017-00608-2. View

Lee S, Lee S, Min B, Oh S . Prognostic implication of systemic inflammatory markers in young patients with resectable colorectal cancer. Ann Surg Treat Res. 2021; 100(1):25-32. PMC: 7791188. DOI: 10.4174/astr.2021.100.1.25. View

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

10.

de Visser K, Korets L, Coussens L . De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell. 2005; 7(5):411-23. DOI: 10.1016/j.ccr.2005.04.014. View

11.

Okiyama N, Tanaka R . Immune-related adverse events in various organs caused by immune checkpoint inhibitors. Allergol Int. 2022; 71(2):169-178. DOI: 10.1016/j.alit.2022.01.001. View

12.

Kovacsovics-Bankowski M, Chisholm L, Vercellini J, Tucker C, Montler R, Haley D . Detailed characterization of tumor infiltrating lymphocytes in two distinct human solid malignancies show phenotypic similarities. J Immunother Cancer. 2014; 2(1):38. PMC: 4247679. DOI: 10.1186/s40425-014-0038-9. View

13.

Takashima Y, Kawaguchi A, Kanayama T, Hayano A, Yamanaka R . Correlation between lower balance of Th2 helper T-cells and expression of PD-L1/PD-1 axis genes enables prognostic prediction in patients with glioblastoma. Oncotarget. 2018; 9(27):19065-19078. PMC: 5922378. DOI: 10.18632/oncotarget.24897. View

14.

Hodi F, ODay S, Mcdermott D, Weber R, Sosman J, Haanen J . Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010; 363(8):711-23. PMC: 3549297. DOI: 10.1056/NEJMoa1003466. View

15.

Gonzalez H, Hagerling C, Werb Z . Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev. 2018; 32(19-20):1267-1284. PMC: 6169832. DOI: 10.1101/gad.314617.118. View

16.

Xu C, Chen Y, Du X, Liu J, Huang C, Chen L . Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis. BMJ. 2018; 363:k4226. PMC: 6222274. DOI: 10.1136/bmj.k4226. View

17.

Routy B, Jackson T, Mahlmann L, Baumgartner C, Blaser M, Byrd A . Melanoma and microbiota: Current understanding and future directions. Cancer Cell. 2023; 42(1):16-34. PMC: 11096984. DOI: 10.1016/j.ccell.2023.12.003. View

18.

Chen L, Kong X, Yan C, Fang Y, Wang J . The Research Progress on the Prognostic Value of the Common Hematological Parameters in Peripheral Venous Blood in Breast Cancer. Onco Targets Ther. 2020; 13:1397-1412. PMC: 7028387. DOI: 10.2147/OTT.S227171. View

19.

Hu Z, Gu X, Zhong R, Zhong H . Tumor-infiltrating CD45RO memory cells correlate with favorable prognosis in patients with lung adenocarcinoma. J Thorac Dis. 2018; 10(4):2089-2099. PMC: 5949455. DOI: 10.21037/jtd.2018.03.148. View

20.

Wu Y, Ye S, Goswami S, Pei X, Xiang L, Zhang X . Clinical significance of peripheral blood and tumor tissue lymphocyte subsets in cervical cancer patients. BMC Cancer. 2020; 20(1):173. PMC: 7057584. DOI: 10.1186/s12885-020-6633-x. View