Mechanisms of tumor escape in the context of the T-cell-inflamed and the non-T-cell-inflamed tumor microenvironment

Int Immunol. 2016 Aug;28(8):383-91. doi: 10.1093/intimm/dxw014. Epub 2016 Mar 17.


Checkpoint blockade therapy has been proven to be highly active across many cancer types but emerging evidence indicates that the therapeutic benefit is limited to a subset of patients in each cancer entity. The presence of CD8(+) T cells within the tumor microenvironment or the invasive margin of the tumor, as well as the up-regulation of PD-L1, have emerged to be the most predictive biomarkers for clinical benefit in response to checkpoint inhibition. Although the up-regulation of immune inhibitory mechanisms is one mechanism of immune escape, commonly used by T-cell-inflamed tumors, exclusion of an anti-tumor specific T-cell infiltrate displays another even more potent mechanism of immune escape. This review will contrast the mechanisms of immunogenic, T-cell-inflamed, and the novel concept of non-immunogenic, non-T-cell-inflamed, adaptive immune escape.

Keywords: checkpoint blockade; immune evasion; immunotherapy; oncogenes.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Humans
  • Immunotherapy / methods*
  • Inflammation / immunology*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • T-Lymphocytes / immunology*
  • Tumor Escape*
  • Tumor Microenvironment