Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells

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...

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Published in:	Immunity (Cambridge, Mass.) Vol. 45; no. 5; pp. 1135 - 1147
Main Authors:	De Simone, Marco, Arrigoni, Alberto, Rossetti, Grazisa, Gruarin, Paola, Ranzani, Valeria, Politano, Claudia, Bonnal, Raoul J.P., Provasi, Elena, Sarnicola, Maria Lucia, Panzeri, Ilaria, Moro, Monica, Crosti, Mariacristina, Mazzara, Saveria, Vaira, Valentina, Bosari, Silvano, Palleschi, Alessandro, Santambrogio, Luigi, Bovo, Giorgio, Zucchini, Nicola, Totis, Mauro, Gianotti, Luca, Cesana, Giancarlo, Perego, Roberto A., Maroni, Nirvana, Pisani Ceretti, Andrea, Opocher, Enrico, De Francesco, Raffaele, Geginat, Jens, Stunnenberg, Hendrik G., Abrignani, Sergio, Pagani, Massimiliano
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 15-11-2016 Elsevier Limited Cell Press
Subjects:	Aged Bioinformatics Cancer therapies Carcinoma, Non-Small-Cell Lung - immunology Carcinoma, Non-Small-Cell Lung - mortality Cell Separation Colorectal cancer Colorectal Neoplasms - immunology Colorectal Neoplasms - mortality Datasets Female Flow Cytometry Gene expression Gene Expression Profiling Humans Kaplan-Meier Estimate Lung cancer Lung Neoplasms - immunology Lung Neoplasms - mortality Lymphocytes Lymphocytes, Tumor-Infiltrating - immunology Male Medical prognosis Metastasis Middle Aged Mortality Polymerase Chain Reaction Prognosis Resource T cell receptors T-Lymphocytes, Regulatory - immunology Transcriptome Tumors
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Summary:	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. •Transcriptome analysis performed on tumor-resident CD4+ Th1, Th17, and Treg cells•Tumor-infiltrating Treg cells are defined by the expression of signature genes•Treg-specific signature genes correlate with patients’ survival in both CRC and NSCLC Tumor-infiltrating regulatory T cells can suppress effector T cells specific for tumor antigens. De Simone et al. (2016) demonstrate that tumor-infiltrating Treg cells display specific gene signatures that were also validated at the single-cell level. These data can contribute to dissect the molecular networks underlying the biology of tumor-infiltrating Treg cells. As part of the IHEC consortium, this study integrates genetic, epigenetic, and transcriptomic profiling in three immune cell types from nearly 200 people to characterize the distinct and cooperative contributions of diverse genomic inputs to transcriptional variation. Explore the Cell Press IHEC webportal at www.cell.com/consortium/IHEC.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Co-first author Lead contact
ISSN:	1074-7613 1097-4180
DOI:	10.1016/j.immuni.2016.10.021