Neoadjuvant Chemotherapy Increases Cytotoxic T Cell, Tissue Resident Memory T Cell, and B Cell Infiltration in Resectable NSCLC
| Autor: | Erin M. Corsini, Junya Fujimoto, Humam Kadara, Ara A. Vaporciyan, Qi Wang, Jing Wang, Ignacio I. Wistuba, Carmen Behrens, Alexandre Reuben, Stephen G. Swisher, Pierre Olivier Gaudreau, Garrett L. Walsh, Lorenzo Federico, Cara Haymaker, Curtis Gumbs, Emily Roarty, Lixia Diao, Jun Li, Edwin Parra-Cuentas, P. Andrew Futreal, Tatiana Karpinets, John V. Heymach, Hai T. Tran, Boris Sepesi, Daniel J. McGrail, Jianhua Zhang, Kyle G. Mitchell, Annikka Weissferdt, Daniel R. Gomez, Don L. Gibbons, Marcelo V. Negrao, Mara B. Antonoff, Chantale Bernatchez, Latasha Little, Roohussaba Khairullah, Tina Cascone, Jianjun Zhang, Arlene M. Correa |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Lung Neoplasms medicine.medical_treatment CD8-Positive T-Lymphocytes Article Flow cytometry 03 medical and health sciences 0302 clinical medicine parasitic diseases Tumor Microenvironment medicine Humans Cytotoxic T cell B cell CD20 B-Lymphocytes Chemotherapy biology medicine.diagnostic_test business.industry Neoadjuvant Therapy Immune checkpoint 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research biology.protein business Immunologic Memory Memory T cell CD8 |
| Zdroj: | J Thorac Oncol |
| ISSN: | 1556-0864 |
| Popis: | Introduction The combination of programmed cell death protein-1 or programmed death-ligand 1 immune checkpoint blockade and chemotherapy has revolutionized the treatment of advanced NSCLC, but the mechanisms underlying this synergy remain incompletely understood. In this study, we explored the relationships between neoadjuvant chemotherapy and the immune microenvironment (IME) of resectable NSCLC to identify novel mechanisms by which chemotherapy may enhance the effect of immune checkpoint blockade. Methods Genomic, transcriptomic, and immune profiling data of 511 patients treated with neoadjuvant chemotherapy followed by surgery (NCT) versus upfront surgery (US) were compared with determined differential characteristics of the IMEs derived from whole-exome sequencing (NCT = 18; US = 73), RNA microarray (NCT = 45; US = 202), flow cytometry (NCT = 17; US = 39), multiplex immunofluorescence (NCT = 10; US = 72), T-cell receptor sequencing (NCT = 16 and US = 63), and circulating cytokines (NCT = 18; US = 73). Results NCT was associated with increased infiltration of cytotoxic CD8+ T cells and CD20+ B cells. Moreover, NCT was associated with increases in CD8+CD103+ and CD4+CD103+PD-1+TIM3− tissue resident memory T cells. Gene expression profiling supported memory function of CD8+ and CD4+ T cells. However, NCT did not affect T-cell receptor clonality, richness, or tumor mutational burden. Finally, NCT was associated with decreased plasma BDNF (TrkB) at baseline and week 4 after surgery. Conclusions Our study supports that, in the context of resectable NSCLC, neoadjuvant chemotherapy promotes antitumor immunity through T and B cell recruitment in the IME and through a phenotypic change toward cytotoxic and memory CD8+ and CD4+ memory helper T cells. |
| Databáze: | OpenAIRE |
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