1. Publications

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 Totis, Luca 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.
Immunity. 2016-11-15;45(5):1135-1147.
Abstract
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.
Consortium data used in this publication
The accession numbers for the data in this paper are as follows: ENA: PRJEB11844 for RNA-seq tumor and tissue infiltrating lymphocytes; ArrayExpress: E-MTAB-2319 for RNA-seq human lymphocytes datasets; ArrayExpress: E-MTAB-513 for Illumina Human BodyMap 2.0 project; GEO: GSE50760 for RNA-seq datasets CRC; GEO: GSE40419 for RNA-seq datasets NSCLC; GEO: GSE17536 for CRC expression profiling by array; and GEO: GSE41271 for NSCLC expression profiling by array.