GPCRs: emerging targets for novel T cell immune checkpoint therapy

Cancer Immunol Immunother. 2024 Oct 3;73(12):253. doi: 10.1007/s00262-024-03801-7.

Abstract

Although immune checkpoint blockade (ICB) has become the mainstay of treatment for advanced solid organ malignancies, success in revitalizing the host anticancer immune response remains limited. G-protein coupled receptors (GPCRs) are a broad family of cell-surface proteins that have been regarded as main players in regulating the immune system, namely by mediating the activity of T lymphocytes. Among the most novel immunoregulatory GPCRs include GPR171, lysophosphatidic acid receptors (LPARs), GPR68, cannabinoid receptor 2 (CB2), and prostaglandin E receptors, many of which have shown promise in mediating antitumor response via activation of cytotoxic T cells, inhibiting immunosuppressive lymphocytes, and facilitating immune cell infiltration within the tumor microenvironment across multiple types of cancers. This paper reviews our current understanding of some of the most novel GPCRs-their expression patterns, evolving roles within the immune system and cancer, potential therapeutic applications, and perspective for future investigation.

Keywords: GPCRs; Immune checkpoint inhibitor; T cell; Tumor immunology.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy / methods
  • Molecular Targeted Therapy / methods
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Receptors, G-Protein-Coupled* / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Microenvironment / immunology

Substances

  • Receptors, G-Protein-Coupled
  • Immune Checkpoint Inhibitors