Pembrolizumab and Chemotherapy Neoadjuvant/Adjuvant of NSCLC

Lung cancer is still the world's leading cancer in terms of mortality. Although the early screening of lung cancer has made great achievements, for example, many lung cancer patients were already in the middle and late stage of lung cancer when they were diagnosed. The majority of patients with resected Stage II and IIIA NSCLC are destined to suffer tumor recurrence despite the administration of standard adjuvant or neoadjuvant therapy. In recent years, neoadjuvant immunotherapy based on PD-1 receptor has provided new opportunities for surgery of locally advanced NSCLC, including the positive results from KEYNOTE-671 and KEYNOTE-091 study. However the mechanism of immunotherapy response and resistance are still less understood. CXCL13+ PD1+ CD8 T cells demonstrate an exhausted phenotype and have been proposed as a surrogate of tumor antigen-specific T cell, a key subset of tumor-infiltrating immune cells that have successfully recognized and killed tumor cells but kept from continued functioning by immune checkpoints including PD-L1. Research on T cell exhaustion in chronic viral infection has also suggested that T cell exhaustion is a result of chronic antigen stimulation, corroborating with the notion that exhausted T cells inside the tumor microenvironment represents successful tumor immune recognition Therefore, in this study, we hypothesize that patients with resectable stage IIA-ⅢB(N2) non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK mutation could benefit from pembrolizumab combined with chemotherapy. Based on the single cell analysis of the pre-treatment and post-treatment samples, we hypothesize that lack of CXCL13+PD1+ T cells is one of the major resistance mechanisms of PD1/PD-L1 blockade.