Multiparametric profiling of non–small-cell lung cancers reveals distinct immunophenotypes

摘要: BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding the diversity NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both and cells from 51 NSCLCs integrated this analysis clinical histopathologic characteristics, next-generation sequencing, mRNA expression, PD-L1 immunohistochemistry (IHC). RESULTS. Cytometric profiling identified an immunologically "hot" cluster abundant CD8+ T expressing high levels TIM-3 "cold" lower relative abundance expression inhibitory markers. The was highly enriched for genes associated cell trafficking cytotoxic function by IHC. There no correlation between immunophenotype KRAS or EGFR mutation, patient smoking history, we did observe enrichment squamous subtype tumors higher mutation burden cluster. Additionally, approximately 20% cases had B infiltrates producing IL-10. CONCLUSIONS. Our results support use immune-based metrics study resistance immunotherapy cancer. FUNDING. Robert A. Renee E. Belfer Family Foundation, Expect Miracles Starr Cancer Consortium, Stand Up Conquer International Association Study Lung Cancer, National Institute (R01 CA205150), Damon Runyon Research Foundation.