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

Myung-Chul Kim, Nicholas Borcherding, Kawther K. Ahmed, Andrew P. Voigt, Ajaykumar Vishwakarma, Ryan Kolb, Paige N. Kluz, Gaurav Pandey, Umasankar De, Theodore 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 () and Weizhou Zhang ()
Additional contact information
Myung-Chul Kim: University of Florida
Nicholas Borcherding: University of Iowa
Kawther K. Ahmed: University of Iowa
Andrew P. Voigt: University of Iowa
Ajaykumar Vishwakarma: University of Iowa
Ryan Kolb: University of Florida
Paige N. Kluz: University of Iowa
Gaurav Pandey: University of Iowa
Umasankar De: University of Florida
Theodore Drashansky: University of Florida College of Medicine, 32610
Eric Y. Helm: University of Florida College of Medicine, 32610
Xin Zhang: University of Florida
Katherine N. Gibson-Corley: Vanderbilt University Medical Center
Julia Klesney-Tait: University of Iowa
Yuwen Zhu: University of Colorado Anschutz Medical Campus
Jinglu Lu: Shanghai Jiao Tong University School of Medicine, Shanghai
Jinsong Lu: Shanghai Jiao Tong University School of Medicine
Xian Huang: Shanghai Jiao Tong University School of Medicine
Hongrui Xiang: Shanghai Jiao Tong University School of Medicine
Jinke Cheng: Shanghai Jiao Tong University School of Medicine
Dongyang Wang: Shanghai Jiao Tong University
Zheng Wang: Shanghai Jiao Tong University
Jian Tang: Shanghai Jiao Tong University
Jiajia Hu: Shanghai Jiao Tong University School of Medicine
Zhengting Wang: Shanghai Jiao Tong University School of Medicine
Hua Liu: Shanghai Jiao Tong University School of Medicine
Mingjia Li: University of Florida
Haoyang Zhuang: University of Florida
Dorina Avram: University of Florida
Daohong Zhou: University of Florida
Rhonda Bacher: University of Florida
Song Guo Zheng: Ohio State University College of Medicine and Wexner Medical Center
Xuefeng Wu: Shanghai Jiao Tong University School of Medicine, Shanghai
Yousef Zakharia: Vanderbilt University Medical Center
Weizhou Zhang: University of Florida

Nature Communications, 2021, vol. 12, issue 1, 1-13

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.

Date: 2021
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DOI: 10.1038/s41467-021-26091-4

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