Impaired Tumor-Infiltrating T Cells in Patients with Chronic Obstructive Pulmonary Disease Impact Lung Cancer Response to PD-1 Blockade

作者：Jérôme Biton, Hanane Ouakrim, Agnès Dechartres, Marco Alifano, Audrey Mansuet‐Lupo, Han Si, Rebecca Halpin, Todd Creasy, Claudie Bantsimba-Malanda, Jennifer Arrondeau, François Goldwasser, Pascaline Boudou‐Rouquette, Ludovic Fournel, Nicolás Roche, Pierre‐Régis Burgel, Jérémy Goc, Priyanka Devi-Marulkar, Claire Germain, Marie‐Caroline Dieu‐Nosjean, Isabelle Cremer, Ronald Herbst, Diane Damotte · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2018 · DOI：10.1164/rccm.201706-1110oc · 被引用次数：101 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Diagnosis and Treatment、Cancer, Stress, Anesthesia, and Immune Response

Abstract Rationale Patients with chronic obstructive pulmonary disease (COPD) have a higher prevalence of lung cancer. The chronic inflammation associated with COPD probably promotes the earliest stages of carcinogenesis. However, once tumors have progressed to malignancy, the impact of COPD on the tumor immune microenvironment remains poorly defined, and its effects on immune-checkpoint blockers’ efficacy are still unknown. Objectives To study the impact of COPD on the immune contexture of non–small cell lung cancer. Methods We performed in-depth immune profiling of lung tumors by immunohistochemistry and we determined its impact on patient survival (n = 435). Tumor-infiltrating T lymphocyte (TIL) exhaustion by flow cytometry (n = 50) was also investigated. The effectiveness of an anti–PD-1 (programmed cell death-1) treatment (nivolumab) was evaluated in 39 patients with advanced-stage non–small cell lung cancer. All data were analyzed according to patient COPD status. Measurements and Main Results Remarkably, COPD severity is positively correlated with the coexpression of PD-1/TIM-3 (T-cell immunoglobulin and mucin domain–containing molecule-3) by CD8 T cells. In agreement, we observed a loss of CD8 T cell–associated favorable clinical outcome in COPD+ patients. Interestingly, a negative prognostic value of PD-L1 (programmed cell death ligand 1) expression by tumor cells was observed only in highly CD8 T cell–infiltrated tumors of COPD+ patients. Finally, data obtained on 3...