Journal article
CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells
Nature communications, Vol.12(1), pp.5764-5764
10/01/2021
DOI: 10.1038/s41467-021-26091-4
PMCID: PMC8486774
PMID: 34599187
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.
Details
- Title: Subtitle
- CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells
- Creators
- Myung-Chul Kim - University of Florida HealthNicholas Borcherding - University of IowaKawther K Ahmed - University of BaghdadAndrew P Voigt - University of IowaAjaykumar Vishwakarma - University of IowaRyan Kolb - University of Florida Health Science CenterPaige N Kluz - University of IowaGaurav Pandey - University of IowaUmasankar De - University of Florida HealthTheodore Drashansky - Florida CollegeEric Y Helm - Florida CollegeXin Zhang - University of Florida HealthKatherine N Gibson-Corley - Vanderbilt University Medical CenterJulia Klesney-Tait - University of IowaYuwen Zhu - University of Colorado Anschutz Medical CampusJinglu Lu - Shanghai Jiao Tong UniversityJinsong Lu - Renji HospitalXian Huang - Shanghai Jiao Tong UniversityHongrui Xiang - Shanghai Jiao Tong UniversityJinke Cheng - State Key Laboratory of Oncogene and Related GenesDongyang Wang - Renji HospitalZheng Wang - Renji HospitalJian Tang - Renji HospitalJiajia Hu - Ruijin HospitalZhengting Wang - Ruijin HospitalHua Liu - Ruijin HospitalMingjia Li - University of FloridaHaoyang Zhuang - University of FloridaDorina Avram - University of Florida HealthDaohong Zhou - University of Florida Health Science CenterRhonda Bacher - University of FloridaSong Guo Zheng - The Ohio State University Wexner Medical CenterXuefeng Wu - Renji HospitalYousef Zakharia - Vanderbilt University Medical CenterWeizhou Zhang - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.12(1), pp.5764-5764
- DOI
- 10.1038/s41467-021-26091-4
- PMID
- 34599187
- PMCID
- PMC8486774
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- T32 GM007337 / NIGMS NIH HHS P30 CA086862 / NCI NIH HHS T32 GM139776 / NIGMS NIH HHS R01 AI067846 / NIAID NIH HHS R01 CA260239 / NCI NIH HHS
- Language
- English
- Date published
- 10/01/2021
- Academic Unit
- Dermatology; Pulmonary, Critical Care, and Occupational Medicine; Hematology, Oncology, and Blood & Marrow Transplantation; The University of Iowa Institute for Vision Research; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984359827902771
Metrics
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