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

Marco De Simone, Alberto Arrigoni, Grazisa Rossetti, Paola Gruarin, Valeria Ranzani, Claudia Politano, Raoul J.P. Bonnal, Elena Provasi, Maria Lucia Sarnicola, Ilaria Panzeri, Monica Moro, Mariacristina Crosti, Saveria Mazzara, Valentina Vaira, Silvano Bosari, Alessandro Palleschi, Luigi Santambrogio, Giorgio Bovo, Nicola Zucchini, Mauro TotisLuca Gianotti, Giancarlo Cesana, Roberto A. Perego, Nirvana Maroni, Andrea Pisani Ceretti, Enrico Opocher, Raffaele De Francesco, Jens Geginat, Hendrik G. Stunnenberg, Sergio Abrignani, Massimiliano Pagani

Research output: Contribution to journalArticlepeer-review

454 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1135-1147
Number of pages13
Issue number5
Publication statusPublished - 15 Nov 2016
Externally publishedYes


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