Targeting innate sensing in the tumor microenvironment to improve immunotherapy

Cell Mol Immunol. 2020 Jan;17(1):13-26. doi: 10.1038/s41423-019-0341-y. Epub 2019 Dec 16.

Abstract

The innate immune sensing pathways play critical roles in the defense against pathogen infection, but their roles in cancer immunosurveillance and cancer therapies are less defined. We propose that defective innate immune sensing inside the tumor microenvironment might limit T-cell responses to immunotherapy. A recent mechanistic understanding of conventional therapies revealed that both innate immune sensing and T-cell responses are essential for optimal antitumor efficacy. T-cell-based immunotherapy, particularly immune checkpoint blockade, has achieved great success in reactivating antitumor immune responses to lead to tumor regression, but only in a small fraction of patients. Therefore, incorporating conventional therapy that can increase innate sensing and immunotherapy should lead to promising strategies for cancer patients. Here, we review the innate sensing pathways related to cancer initiation/progression and therapies, summarize the recent key findings in innate immune sensing related to conventional therapies, evaluate current combination strategies, and highlight the potential issues of combinational therapies in terms of antitumor efficacy and toxicities.

Keywords: Conventional therapy; Immunotherapy; Innate immune sensing.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunity, Cellular / drug effects*
  • Immunity, Innate / drug effects*
  • Immunotherapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / immunology

Substances

  • Immune Checkpoint Inhibitors