TIM-3: An update on immunotherapy

Int Immunopharmacol. 2021 Oct:99:107933. doi: 10.1016/j.intimp.2021.107933. Epub 2021 Jul 2.

Abstract

T cell immunoglobulin and mucin domain 3 (TIM-3) was originally found to be expressed on the surface of Th1 cells, acting as a negative regulator and binding to the ligand galectin-9 to mediate Th1 cell the apoptosis. Recent studies have shown that TIM-3 is also expressed on other immune cells, such as macrophages, dendritic cells, and monocytes. In addition, TIM-3 ligands also include Psdter, High Mobility Group Box 1 (HMGB1) and Carcinoembryonic antigen associated cell adhesion molecules (Ceacam-1), which have different effects upon biding to different ligands on immune cells. Studies have shown that TIM-3 plays an important role in autoimmune diseases, chronic viral infections and tumors. A large amount of experimental data supports TIM-3 as an immune checkpoint, and targeting TIM-3 is a promising treatment method in current immunotherapy, especially the new combination of other immune checkpoint blockers. In this review, we summarize the role of TIM-3 in different diseases and its possible signaling pathway mechanisms, providing new insights for better breakthrough immunotherapy.

Keywords: Autoimmune diseases; Gal-9; TIM-3; Tumors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Autoimmune Diseases / metabolism*
  • Biomarkers / metabolism*
  • Carcinoembryonic Antigen / metabolism
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Galectins / metabolism
  • Glycosylation
  • HMGB1 Protein / metabolism
  • Hepatitis A Virus Cellular Receptor 2 / metabolism*
  • Humans
  • Immune Checkpoint Inhibitors / metabolism*
  • Immune Tolerance
  • Immunotherapy
  • Ligands
  • Neoplasms / metabolism*
  • Protein Binding
  • Signal Transduction
  • Th1 Cells
  • Virus Diseases / metabolism*

Substances

  • Antigens, CD
  • Biomarkers
  • CD66 antigens
  • Carcinoembryonic Antigen
  • Cell Adhesion Molecules
  • Galectins
  • HAVCR2 protein, human
  • HMGB1 Protein
  • HMGB1 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Immune Checkpoint Inhibitors
  • LGALS9 protein, human
  • Ligands