Classification of Tumor Immune Microenvironment According to Programmed Death-Ligand 1 Expression and Immune Infiltration Predicts Response to Immunotherapy Plus Chemotherapy in Advanced Patients With NSCLC

作者：Dongchen Sun, Jiaqing Liu, Huaqiang Zhou, Mengting Shi, Jiya Sun, Shen Zhao, Gang Chen, Yaxiong Zhang, Ting Zhou, Yuxiang Ma, Yuanyuan Zhao, Wen‐Feng Fang, Hongyun Zhao, Yan Huang, Yunpeng Yang, Li Zhang · 发表于：Journal of Thoracic Oncology · 年份：2023 · DOI：10.1016/j.jtho.2023.03.012 · 被引用次数：90 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Inflammatory Biomarkers in Disease Prognosis

INTRODUCTION: According to mechanisms of adaptive immune resistance, tumor immune microenvironment (TIME) is classified into four types: (1) programmed death-ligand 1 (PD-L1)-negative and tumor-infiltrating lymphocyte (TIL)-negative (type I); (2) PD-L1-positive and TIL-positive (type II); (3) PD-L1-negative and TIL-positive (type III); and (4) PD-L1-positive and TIL-negative (type IV). However, the relationship between the TIME classification model and immunotherapy efficacy has not been validated by any large-scale randomized controlled clinical trial among patients with advanced NSCLC. METHODS: On the basis of RNA-sequencing and immunohistochemistry data from the ORIENT-11 study, we optimized the TIME classification model and evaluated its predictive value for the efficacy of immunotherapy plus chemotherapy. RESULTS: PD-L1 mRNA expression and immune score calculated by the ESTIMATE method were the strongest predictors for the efficacy of immunotherapy plus chemotherapy. Therefore, they were determined as the optimized definition of the TIME classification system. When compared between combination therapy and chemotherapy alone, only the type II subpopulation with high immune score and high PD-L1 mRNA expression was significantly associated with improved progression-free survival (PFS) (hazard ratio = 0.12, 95% confidence interval: 0.06-0.25, p < 0.001) and overall survival (hazard ratio = 0.27, 95% confidence interval: 0.13-0.55, p < 0.001). In the combination group, the ty...