期刊
IMMUNITY
卷 45, 期 5, 页码 1135-1147出版社
CELL PRESS
DOI: 10.1016/j.immuni.2016.10.021
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资金
- Italian Minister of Health [GR2011-02351626]
- AIRC [IG2015-ID17448, IG2013-ID14596]
- Italian Minister of University and Research Grant [CTN01_00177_817708]
- ERC Advanced Grant [269022]
- Flagship CNR-MIUR grant EPIGEN, CARIPLO [2013-0955]
- ERC Consolidator Grant [617978]
- Fondazione Romeo ed Enrica Invernizzi
- Research Grant DNA on Disk [CTN01_00177_817708]
- European Research Council (ERC) [617978, 269022] Funding Source: European Research Council (ERC)
Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deepermolecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or non-small-cell lung cancers were compared to transcriptomes of the same subsets from normal tissues and validated at the single-cell level. We found that tumor-infiltrating Treg cells were highly suppressive, upregulated several immune-checkpoints, and expressed on the cell surfaces specific signature molecules such as interleukin-1 receptor 2 (IL1R2), programmed death (PD)-1 Ligand1, PD-1 Ligand2, and CCR8 chemokine, which were not previously described on Treg cells. Remarkably, high expression in whole-tumor samples of Treg cell signature genes, such as LAYN, MAGEH1, or CCR8, correlated with poor prognosis. Our findings provide insights into the molecular identity and functions of human tumor-infiltrating Treg cells and define potential targets for tumor immunotherapy.
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