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Immunity. 2016 Nov 15;45(5):1135-1147. doi: 10.1016/j.immuni.2016.10.021.

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

Author information

1
Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
2
Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy; Division of Pathology, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy; Department of Pathophysiology and Organ Transplantation, Università degli Studi di Milano, Milano 20122, Italy.
3
Division of Pathology, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy; Department of Pathophysiology and Organ Transplantation, Università degli Studi di Milano, Milano 20122, Italy.
4
Division of Thoracic Surgery, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.
5
Division of Thoracic Surgery, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy; Department of Pathophysiology and Organ Transplantation, Università degli Studi di Milano, Milano 20122, Italy.
6
Department of Pathology, San Gerardo Hospital, Monza 20900, Italy.
7
Department of Surgery, San Gerardo Hospital, Monza 20900, Italy.
8
Department of Surgery, San Gerardo Hospital, Monza 20900, Italy; School of Medicine and Surgery, Milano-Bicocca University, Monza 20900 Italy.
9
School of Medicine and Surgery, Milano-Bicocca University, Monza 20900 Italy.
10
UO Chirurgia Epatobiliopancreatica e Digestiva Ospedale San Paolo, Milan 20142, Italy.
11
UO Chirurgia Epatobiliopancreatica e Digestiva Ospedale San Paolo, Milan 20142, Italy; Department of Health Sciences, Università degli Studi di Milano, Milano 20122, Italy.
12
Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen, The Netherlands.
13
Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano 20122, Italy. Electronic address: abrignani@ingm.org.
14
Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milano 20129, Italy. Electronic address: pagani@ingm.org.

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.

PMID:
27851914
PMCID:
PMC5119953
DOI:
10.1016/j.immuni.2016.10.021
[Indexed for MEDLINE]
Free PMC Article

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