The GPR171 pathway suppresses T cell activation and limits antitumor immunity

Yuki Fujiwara, Robert J. Torphy, Yi Sun, Emily N. Miller, Felix Ho, Nicholas Borcherding, Tuoqi Wu, Raul M. Torres, Weizhou Zhang, Richard D. Schulick and Yuwen Zhu ()
Additional contact information
Yuki Fujiwara: University of Colorado Anschutz Medical Campus
Robert J. Torphy: University of Colorado Anschutz Medical Campus
Yi Sun: University of Colorado Anschutz Medical Campus
Emily N. Miller: University of Colorado Anschutz Medical Campus
Felix Ho: University of Colorado Anschutz Medical Campus
Nicholas Borcherding: Washington University
Tuoqi Wu: University of Colorado Anschutz Medical Campus
Raul M. Torres: University of Colorado Anschutz Medical Campus
Weizhou Zhang: University of Florida
Richard D. Schulick: University of Colorado Anschutz Medical Campus
Yuwen Zhu: University of Colorado Anschutz Medical Campus

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26135-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26135-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26135-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().