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CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells.
Kim, Myung-Chul; Borcherding, Nicholas; Ahmed, Kawther K; Voigt, Andrew P; Vishwakarma, Ajaykumar; Kolb, Ryan; Kluz, Paige N; Pandey, Gaurav; De, Umasankar; Drashansky, Theodore; Helm, Eric Y; Zhang, Xin; Gibson-Corley, Katherine N; Klesney-Tait, Julia; Zhu, Yuwen; Lu, Jinglu; Lu, Jinsong; Huang, Xian; Xiang, Hongrui; Cheng, Jinke; Wang, Dongyang; Wang, Zheng; Tang, Jian; Hu, Jiajia; Wang, Zhengting; Liu, Hua; Li, Mingjia; Zhuang, Haoyang; Avram, Dorina; Zhou, Daohong; Bacher, Rhonda; Zheng, Song Guo; Wu, Xuefeng; Zakharia, Yousef; Zhang, Weizhou.
Afiliação
  • Kim MC; Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, 32610, USA.
  • Borcherding N; UF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA.
  • Ahmed KK; Department of Pathology, University of Iowa, Iowa City, IA, 52242, USA.
  • Voigt AP; Cancer Biology Graduate Program, University of Iowa, Iowa City, IA, 52242, USA.
  • Vishwakarma A; Medical Scientist Training Program, University of Iowa, Iowa City, IA, 52242, USA.
  • Kolb R; Department of Pathology, University of Iowa, Iowa City, IA, 52242, USA.
  • Kluz PN; College of Pharmacy, University of Baghdad, Department of Pharmaceutics, Baghdad, 10071, Iraq.
  • Pandey G; Medical Scientist Training Program, University of Iowa, Iowa City, IA, 52242, USA.
  • De U; Cancer Biology Graduate Program, University of Iowa, Iowa City, IA, 52242, USA.
  • Drashansky T; Department of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, IA52242, USA.
  • Helm EY; Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, 32610, USA.
  • Zhang X; UF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA.
  • Gibson-Corley KN; Department of Pathology, University of Iowa, Iowa City, IA, 52242, USA.
  • Klesney-Tait J; Department of Pathology, University of Iowa, Iowa City, IA, 52242, USA.
  • Zhu Y; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Lu J; Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, 32610, USA.
  • Lu J; UF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA.
  • Huang X; Department of Anatomy and Cell Biology, University of Florida College of Medicine, 32610, Gainesville, FL, 32610, USA.
  • Xiang H; Department of Anatomy and Cell Biology, University of Florida College of Medicine, 32610, Gainesville, FL, 32610, USA.
  • Cheng J; UF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA.
  • Wang D; Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Fl, 32610, USA.
  • Wang Z; Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232-2130, USA.
  • Tang J; Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.
  • Hu J; Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
  • Wang Z; Department of Breast Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, Shanghai, 200127, China.
  • Liu H; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • Li M; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • Zhuang H; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • Avram D; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • Zhou D; State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • Bacher R; Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
  • Zheng SG; Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
  • Wu X; Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
  • Zakharia Y; Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • Zhang W; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Nat Commun ; 12(1): 5764, 2021 10 01.
Article em En | MEDLINE | ID: mdl-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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos do Interstício Tumoral / Linfócitos T Reguladores / Receptores de Superfície Celular / Proteínas Ligadas por GPI / Homeostase / Isoantígenos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos do Interstício Tumoral / Linfócitos T Reguladores / Receptores de Superfície Celular / Proteínas Ligadas por GPI / Homeostase / Isoantígenos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article