Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells
OPEN Immunity | 17 Nov 2016
M De Simone, A Arrigoni, G Rossetti, P Gruarin, V Ranzani, C Politano, RJ Bonnal, E Provasi, ML Sarnicola, I Panzeri, M Moro, M Crosti, S Mazzara, V Vaira, S Bosari, A Palleschi, L Santambrogio, G Bovo, N Zucchini, M Totis, L Gianotti, G Cesana, RA Perego, N Maroni, A Pisani Ceretti, E Opocher, R De Francesco, J Geginat, HG Stunnenberg, S Abrignani and M Pagani
Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular 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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