Tumor fitness, immune exhaustion and clinical outcomes: impact of immune checkpoint inhibitors

Recently proposed tumor fitness measures, based on profiling neoepitopes for reactive viral epitope similarity, have led to improved prediction models of response to immune checkpoint inhibitors in melanoma and small-cell lung cancer. Here we test if this checkpoint based fitness is associated with tumor T-cell infiltration, cytolytic activity (CYT), and abundance (TIL burden) in the treatment naive samples from the same tumor types using data from TCGA. We find no significant correlation between TIL burden or CYT and the proposed neoepitope based fitness measures. Similarly, no significant survival predictive power beyond that of overall patient tumor mutation burden in either cohort is observed. Further, we find suggestive evidence that tumor neoepitopes dominate viral epitopes in putative immunogenicity and drives immune response in liver cancer with hepatitis B virus infection (HBV) in the TCGA.