Tumor-intrinsic signaling pathways: key roles in the regulation of the immunosuppressive tumor microenvironment

J Hematol Oncol. 2019 Nov 27;12(1):125. doi: 10.1186/s13045-019-0804-8.

Abstract

Immunotherapy is a currently popular treatment strategy for cancer patients. Although recent developments in cancer immunotherapy have had significant clinical impact, only a subset of patients exhibits clinical response. Therefore, understanding the molecular mechanisms of immunotherapy resistance is necessary. The mechanisms of immune escape appear to consist of two distinct tumor characteristics: a decrease in effective immunocyte infiltration and function and the accumulation of immunosuppressive cells in the tumor microenvironment. Several host-derived factors may also contribute to immune escape. Moreover, inter-patient heterogeneity predominantly results from differences in somatic mutations between cancers, which has led to the hypothesis that differential activation of specific tumor-intrinsic pathways may explain the phenomenon of immune exclusion in a subset of cancers. Increasing evidence has also shown that tumor-intrinsic signaling plays a key role in regulating the immunosuppressive tumor microenvironment and tumor immune escape. Therefore, understanding the mechanisms underlying immune avoidance mediated by tumor-intrinsic signaling may help identify new therapeutic targets for expanding the efficacy of cancer immunotherapies.

Keywords: Immune escape; Immunosuppressive cells; Immunosuppressive tumor microenvironment; T cell infiltration; Tumor-intrinsic signaling.

Publication types

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

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Immunotherapy / methods*
  • Molecular Targeted Therapy / methods*
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Signal Transduction
  • Tumor Escape / drug effects
  • Tumor Escape / immunology*
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology*

Substances

  • Antineoplastic Agents
  • Immunosuppressive Agents