CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells
Myung‐Chul Kim, Nicholas Borcherding, Kawther Khalid Ahmed, Andrew P. Voigt, Ajaykumar Vishwakarma, Ryan Kolb, Paige Kluz, Gaurav Pandey, Umasankar De, Theodore T. Drashansky, Eric Y. Helm, Xin Zhang, Katherine N. Gibson‐Corley, Julia Klesney‐Tait, Yuwen Zhu, Jinglu Lu, Jinsong Lu, Xian Huang, Hongrui Xiang, Jinke Cheng, Dongyang Wang, Zheng Wang, Jian Tang, Jiajia Hu, Zhengting Wang, Hua Liu, Mingjia Li, Haoyang Zhuang, Dorina Avram, Daohong Zhou, Rhonda Bacher, Song Guo Zheng, Xuefeng Wu, Yousef Zakharia, Weizhou Zhang
Abstract
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.