2. Academic Validation
  3. The GPR171 pathway suppresses T cell activation and limits antitumor immunity

The GPR171 pathway suppresses T cell activation and limits antitumor immunity

  • Nat Commun. 2021 Oct 6;12(1):5857. doi: 10.1038/s41467-021-26135-9.
Yuki Fujiwara 1,  Robert J Torphy 1,  Yi Sun 1,  Emily N Miller 1,  Felix Ho 1,  Nicholas Borcherding 2,  Tuoqi Wu 3,  Raul M Torres 3,  Weizhou Zhang 4,  Richard D Schulick 1,  Yuwen Zhu 5
Affiliations

Affiliations

  • 1 Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
  • 2 Department of Pathology and Immunology, Washington University, St. Louis, MO, 63110, USA.
  • 3 Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
  • 4 Department of Pathology, University of Florida, Gainesville, FL, 32610, USA.
  • 5 Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. yuwen.zhu@cuanschutz.edu.
PMID: 34615877 DOI: 10.1038/s41467-021-26135-9
Abstract

The recently identified G-protein-coupled receptor GPR171 and its ligand BigLEN are thought to regulate food uptake and anxiety. Though GPR171 is commonly used as a T cell signature gene in transcriptomic studies, its potential role in T cell immunity has not been explored. Here we show that GPR171 is transcribed in T cells and its protein expression is induced upon antigen stimulation. The neuropeptide ligand BigLEN interacts with GPR171 to suppress T cell receptor-mediated signalling pathways and to inhibit T cell proliferation. Loss of GPR171 in T cells leads to hyperactivity to antigen stimulation and GPR171 knockout mice exhibit enhanced antitumor immunity. Blockade of GPR171 signalling by an antagonist promotes antitumor T cell immunity and improves Immune Checkpoint blockade therapies. Together, our study identifies the GPR171/BigLEN axis as a T cell checkpoint pathway that can be modulated for Cancer Immunotherapy.

Figures