CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34599187.
- Also identified by DOI 10.1038/s41467-021-26091-4 and PMC identifier 8486774.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- GPI-Linked Proteins
- Homeostasis
- Isoantigens
- Lymphocytes, Tumor-Infiltrating
- Receptors, Cell Surface
- T-Lymphocytes, Regulatory