TREM2: Keeping Pace With Immune Checkpoint Inhibitors in Cancer Immunotherapy

Front Immunol. 2021 Sep 3:12:716710. doi: 10.3389/fimmu.2021.716710. eCollection 2021.

Abstract

To date, immune checkpoint inhibitors have been successively approved and widely used in clinical cancer treatments, however, the overall response rates are very low and almost all cancer patients eventually progressed to drug resistance, this is mainly due to the intricate tumor microenvironment and immune escape mechanisms of cancer cells. One of the main key mechanisms leading to the evasion of immune attack is the presence of the immunosuppressive microenvironment within tumors. Recently, several studies illustrated that triggering receptor expressed on myeloid cells-2 (TREM2), a transmembrane receptor of the immunoglobulin superfamily, was a crucial pathology-induced immune signaling hub, and it played a vital negative role in antitumor immunity, such as inhibiting the proliferation of T cells. Here, we reviewed the recent advances in the study of TREM2, especially focused on its regulation of tumor-related immune signaling pathways and its role as a novel target in cancer immunotherapy.

Keywords: TREM2; cancer immunotherapy; immune checkpoint inhibitor; immune microenvironment; immunosuppressive myeloid cell.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immune Checkpoint Proteins / genetics
  • Immune Checkpoint Proteins / metabolism
  • Immunotherapy / methods
  • Immunotherapy / mortality
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Molecular Targeted Therapy
  • Neoplasms / diagnosis
  • Neoplasms / etiology
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / metabolism*
  • Signal Transduction / drug effects
  • Structure-Activity Relationship
  • Tumor Microenvironment / immunology

Substances

  • Antineoplastic Agents, Immunological
  • Immune Checkpoint Inhibitors
  • Immune Checkpoint Proteins
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • TREM2 protein, human