Earlier-Phased Cancer Immunity Cycle Strongly Influences Cancer Immunity in Operable Never-Smoker Lung Adenocarcinoma

Exome and transcriptome analyses of clinically homogeneous early-stage never-smoker female patients with lung adenocarcinoma were performed to understand tumor-T cell interactions and immune escape points. Using our novel gene panels of eight functional categories in the cancer-immunity cycle, three distinct subgroups were identified in this immune checkpoint blockade-refractory cohort by defective gene expression in two major domains, i.e., type I interferon production/signaling pathway and antigen-presenting machinery. Our approach could play a critical role in understanding immune evasion mechanisms, developing a method for effective selection of rare immune checkpoint blockade responders, and finding new treatment strategies. [Display omitted] •GMM-based clustering of cancer-immune gene expression helps to find LUAD classifiers•Classifiers are found in the earlier-phased cancer-immunity cycle•Classifiers include ubiquitination, Ag-presenting machinery, and type I IFN signaling•Tumor-intrinsic classifiers strongly influence the outcome of cancer immunity Immunology; Cancer Systems Biology; Genomics