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CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells
Journal article   Open access   Peer reviewed

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, …
Nature communications, Vol.12(1), pp.5764-5764
10/01/2021
DOI: 10.1038/s41467-021-26091-4
PMCID: PMC8486774
PMID: 34599187
url
https://doi.org/10.1038/s41467-021-26091-4View
Published (Version of record) Open Access

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.
Animals Base Sequence Carcinogenesis - genetics Carcinogenesis - pathology Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - immunology Carcinoma, Renal Cell - pathology Gene Expression Profiling Gene Expression Regulation, Neoplastic GPI-Linked Proteins - deficiency GPI-Linked Proteins - metabolism Homeostasis Humans Isoantigens - metabolism Kidney Neoplasms - genetics Kidney Neoplasms - immunology Kidney Neoplasms - pathology Lymphocytes, Tumor-Infiltrating - metabolism Mice, Knockout Prognosis Receptors, Cell Surface - deficiency Receptors, Cell Surface - metabolism Single-Cell Analysis T-Lymphocytes, Regulatory - metabolism Transcription, Genetic

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