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

Sci Rep. 2020 Mar 19;10(1):5062. doi: 10.1038/s41598-020-61992-2.

Abstract

Recently proposed tumor fitness measures, based on profiling neoepitopes for reactive viral epitope similarity, have been proposed to predict response to immune checkpoint inhibitors in melanoma and small-cell lung cancer. Here we applied these checkpoint based fitness measures to the matched checkpoint treatment naive Cancer Genome Atlas (TCGA) samples where cytolytic activity (CYT) imparts a known survival benefit. We observed no significant survival predictive power beyond that of overall patient tumor mutation burden, and furthermore, found no association between checkpoint based fitness and tumor T-cell infiltration, cytolytic activity, and abundance (tumor infiltrating lymphocyte, TIL, burden). In addition, we investigated the key assumption of viral epitope similarity driving immune response in the hepatitis B virally infected liver cancer TCGA cohort, and uncovered suggestive evidence that tumor neoepitopes actually dominate viral epitopes in putative immunogenicity and plausibly drive immune response and recruitment.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cohort Studies
  • Epitopes
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunotherapy*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / immunology*
  • Melanoma / pathology
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / pathology
  • T-Lymphocytes / immunology
  • Treatment Outcome

Substances

  • Epitopes
  • Immune Checkpoint Inhibitors