TY - JOUR
T1 - CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells
AU - Kim, Myung Chul
AU - Borcherding, Nicholas
AU - Ahmed, Kawther K.
AU - Voigt, Andrew P.
AU - Vishwakarma, Ajaykumar
AU - Kolb, Ryan
AU - Kluz, Paige N.
AU - Pandey, Gaurav
AU - De, Umasankar
AU - Drashansky, Theodore
AU - Helm, Eric Y.
AU - Zhang, Xin
AU - Gibson-Corley, Katherine N.
AU - Klesney-Tait, Julia
AU - Zhu, Yuwen
AU - Lu, Jinglu
AU - Lu, Jinsong
AU - Huang, Xian
AU - Xiang, Hongrui
AU - Cheng, Jinke
AU - Wang, Dongyang
AU - Wang, Zheng
AU - Tang, Jian
AU - Hu, Jiajia
AU - Wang, Zhengting
AU - Liu, Hua
AU - Li, Mingjia
AU - Zhuang, Haoyang
AU - Avram, Dorina
AU - Zhou, Daohong
AU - Bacher, Rhonda
AU - Zheng, Song Guo
AU - Wu, Xuefeng
AU - Zakharia, Yousef
AU - Zhang, Weizhou
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85116352676&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-26091-4
DO - 10.1038/s41467-021-26091-4
M3 - Article
C2 - 34599187
AN - SCOPUS:85116352676
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5764
ER -