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CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells

Authors :
Zheng Wang
Dorina Avram
Xin Zhang
Ryan Kolb
Ajaykumar Vishwakarma
Hongrui Xiang
Xuefeng Wu
Xian Huang
Katherine N. Gibson-Corley
Umasankar De
Andrew P. Voigt
Julia Klesney-Tait
Myung-Chul Kim
Dongyang Wang
Song Guo Zheng
Mingjia Li
Rhonda Bacher
Weizhou Zhang
Gaurav Pandey
Nicholas Borcherding
Jiajia Hu
Jian Tang
Haoyang Zhuang
Jinke Cheng
Yuwen Zhu
Daohong Zhou
Jinglu Lu
Theodore T. Drashansky
Paige Kluz
Kawther K. Ahmed
Yousef Zakharia
Zhengting Wang
Hua Liu
Eric Y. Helm
Jinsong Lu
Source :
Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021), Nature Communications
Publication Year :
2021
Publisher :
Nature Portfolio, 2021.

Abstract

Regulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers. CD177, a cell surface protein normally expressed on neutrophil, is specifically expressed on Fate-1 TI Treg cells in several solid cancer types, but not on other TI or peripheral Treg cells. Mechanistically, blocking CD177 reduces the suppressive activity of Treg cells in vitro, while Treg-specific deletion of Cd177 leads to decreased tumor growth and reduced TI Treg frequency in mice. Our results thus uncover a functional CD177+ TI Treg population that may serve as a target for TI Treg-specific immunotherapy.<br />Regulatory T (Treg) cells are important modulators of the tumor microenvironment. Here the authors perform transcriptome profiling of immune cells from patients with renal clear cell carcinoma to find a Treg signature that correlates with poorer prognosis, with CD177 being implicated as the main mediator for related alterations in Treg activity and tumor outcome.

Details

Language :
English
ISSN :
20411723
Volume :
12
Issue :
1
Database :
OpenAIRE
Journal :
Nature Communications
Accession number :
edsair.doi.dedup.....926e3a2cc612c6ab949c8e15fe695d1c