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

Author

Listed:
  • Myung-Chul Kim

    (University of Florida
    University of Florida)

  • Nicholas Borcherding

    (University of Iowa
    University of Iowa
    University of Iowa)

  • Kawther K. Ahmed

    (University of Iowa
    University of Baghdad, Department of Pharmaceutics)

  • Andrew P. Voigt

    (University of Iowa)

  • Ajaykumar Vishwakarma

    (University of Iowa
    University of Iowa)

  • Ryan Kolb

    (University of Florida
    University of Florida)

  • Paige N. Kluz

    (University of Iowa)

  • Gaurav Pandey

    (University of Iowa
    Washington University School of Medicine)

  • Umasankar De

    (University of Florida
    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
    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
    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
    University of Florida College of Medicine, 32610
    Moffitt Cancer Center)

  • Daohong Zhou

    (University of Florida
    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
    Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Yousef Zakharia

    (Vanderbilt University Medical Center)

  • Weizhou Zhang

    (University of Florida
    University of Florida
    University of Iowa)

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.

Suggested Citation

  • 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, 2021. "CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26091-4
    DOI: 10.1038/s41467-021-26091-4
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