Journal Article
. 2021 Oct; 12(1):5764.
doi: 10.1038/s41467-021-26091-4.

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

Myung-Chul Kim 1 Nicholas Borcherding 2 Kawther K Ahmed 2 Andrew P Voigt 3 Ajaykumar Vishwakarma 4 Ryan Kolb 1 Paige N Kluz 2 Gaurav Pandey 2 Umasankar De 1 Theodore Drashansky 5 Eric Y Helm 5 Xin Zhang 6 Katherine N Gibson-Corley 7 Julia Klesney-Tait 8 Yuwen Zhu 9 Jinglu Lu 10 Jinsong Lu 11 Xian Huang 11 Hongrui Xiang 11 Jinke Cheng 12 Dongyang Wang 13 Zheng Wang 13 Jian Tang 13 Jiajia Hu 14 Zhengting Wang 15 Hua Liu 15 Mingjia Li 16 Haoyang Zhuang 16 Dorina Avram 6 Daohong Zhou 6 Rhonda Bacher 17 Song Guo Zheng 18 Xuefeng Wu 19 Yousef Zakharia 20 Weizhou Zhang 21 
Affiliations
  • PMID: 34599187
  •     44 References
  •     1 citations

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.

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