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; Weizhou Zhang

doi:10.1038/s41467-021-26091-4

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, Weizhou Zhang

Producción científica: Article › revisión exhaustiva

77 Citas (Scopus)

Resumen

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.

Idioma original	English (US)
Número de artículo	5764
Publicación	Nature communications
Volumen	12
N.º	1
DOI	https://doi.org/10.1038/s41467-021-26091-4
Estado	Published - dic 1 2021
Publicado de forma externa	Sí

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-021-26091-4

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Kim, M. C., Borcherding, N., Ahmed, K. K., Voigt, A. P., Vishwakarma, A., Kolb, R., Kluz, P. N., Pandey, G., De, U., Drashansky, T., Helm, E. Y., Zhang, X., Gibson-Corley, K. N., Klesney-Tait, J., Zhu, Y., Lu, J., Lu, J., Huang, X., Xiang, H., ... Zhang, W. (2021). CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells. Nature communications, 12(1), Artículo 5764. https://doi.org/10.1038/s41467-021-26091-4

Kim, MC, Borcherding, N, Ahmed, KK, Voigt, AP, Vishwakarma, A, Kolb, R, Kluz, PN, Pandey, G, De, U, Drashansky, T, Helm, EY, Zhang, X, Gibson-Corley, KN, Klesney-Tait, J, Zhu, Y, Lu, J, Lu, J, Huang, X, Xiang, H, Cheng, J, Wang, D, Wang, Z, Tang, J, Hu, J, Wang, Z, Liu, H, Li, M, Zhuang, H, Avram, D, Zhou, D, Bacher, R, Zheng, SG, Wu, X, Zakharia, Y & Zhang, W 2021, 'CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells', Nature communications, vol. 12, n.º 1, 5764. https://doi.org/10.1038/s41467-021-26091-4

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title = "CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells",

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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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

PY - 2021/12/1

Y1 - 2021/12/1

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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.

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

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ASJC Scopus subject areas

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