TY - JOUR
T1 - Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells
AU - De Simone, Marco
AU - Arrigoni, Alberto
AU - Rossetti, Grazisa
AU - Gruarin, Paola
AU - Ranzani, Valeria
AU - Politano, Claudia
AU - Bonnal, Raoul J.P.
AU - Provasi, Elena
AU - Sarnicola, Maria Lucia
AU - Panzeri, Ilaria
AU - Moro, Monica
AU - Crosti, Mariacristina
AU - Mazzara, Saveria
AU - Vaira, Valentina
AU - Bosari, Silvano
AU - Palleschi, Alessandro
AU - Santambrogio, Luigi
AU - Bovo, Giorgio
AU - Zucchini, Nicola
AU - Totis, Mauro
AU - Gianotti, Luca
AU - Cesana, Giancarlo
AU - Perego, Roberto A.
AU - Maroni, Nirvana
AU - Pisani Ceretti, Andrea
AU - Opocher, Enrico
AU - De Francesco, Raffaele
AU - Geginat, Jens
AU - Stunnenberg, Hendrik G.
AU - Abrignani, Sergio
AU - Pagani, Massimiliano
N1 - Publisher Copyright:
© 2016 The Author(s)
PY - 2016/11/15
Y1 - 2016/11/15
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84999673353
U2 - 10.1016/j.immuni.2016.10.021
DO - 10.1016/j.immuni.2016.10.021
M3 - Article
C2 - 27851914
AN - SCOPUS:84999673353
SN - 1074-7613
VL - 45
SP - 1135
EP - 1147
JO - Immunity
JF - Immunity
IS - 5
ER -