CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells.
Myung-Chul KimNicholas BorcherdingKawther Khalid AhmedAndrew P VoigtAjaykumar VishwakarmaRyan KolbPaige N KluzGaurav PandeyUmasankar DeTheodore T DrashanskyEric Y HelmXin ZhangKatherine N Gibson-CorleyJulia Klesney-TaitYuwen ZhuJinglu LuJinsong LuXian HuangHongrui XiangJinke ChengDongyang WangZheng WangJian TangJiajia HuZhengting WangHua LiuMingjia LiHaoyang ZhuangDorina AvramDaohong ZhouRhonda BacherSong Guo ZhengXuefeng WuYousef ZakhariaWeizhou ZhangPublished in: Nature communications (2021)
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.
Keyphrases
- induced apoptosis
- single cell
- cell cycle arrest
- regulatory t cells
- oxidative stress
- endoplasmic reticulum stress
- gene expression
- stem cells
- end stage renal disease
- type diabetes
- signaling pathway
- risk assessment
- metabolic syndrome
- adipose tissue
- dendritic cells
- ejection fraction
- skeletal muscle
- cancer therapy
- papillary thyroid
- squamous cell
- binding protein
- patient reported
- heat shock protein