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

被引：579

作者：

De Simone, Marco ^{[1
]}

Arrigoni, Alberto ^{[1
]}

Rossetti, Grazisa ^{[1
]}

Gruarin, Paola ^{[1
]}

Ranzani, Valeria ^{[1
]}

Politano, Claudia ^{[1
]}

Bonnal, Raoul J. P. ^{[1
]}

Provasi, Elena ^{[1
]}

Sarnicola, Maria Lucia ^{[1
]}

Panzeri, Ilaria ^{[1
]}

Moro, Monica ^{[1
]}

Crosti, Mariacristina ^{[1
]}

Mazzara, Saveria ^{[1
]}

Vaira, Valentina ^{[1
,2
,4
]}

Bosari, Silvano ^{[2
,4
]}

Palleschi, Alessandro ^{[3
]}

Santambrogio, Luigi ^{[3
,4
]}

Bovo, Giorgio ^{[5
]}

Zucchini, Nicola ^{[5
]}

Totis, Mauro ^{[6
]}

Gianotti, Luca ^{[6
,7
]}

Cesana, Giancarlo ^{[7
]}

Perego, Roberto A. ^{[7
]}

Maroni, Nirvana ^{[8
]}

Ceretti, Andrea Pisani ^{[8
]}

Opocher, Enrico ^{[8
,9
]}

De Francesco, Raffaele ^{[1
]}

Geginat, Jens ^{[1
]}

Stunnenberg, Hendrik G. ^{[10
]}

Abrignani, Sergio ^{[1
,11
]}

Pagani, Massimiliano ^{[1
,12
]}

机构：

[1] Ist Nazl Genet Mol INGM Romeo & Enrica Invernizzi, I-20122 Milan, Italy

[2] IRCCS Ca Granda Osped Maggiore Policlin, Div Pathol, I-20122 Milan, Italy

[3] IRCCS Ca Granda Osped Maggiore Policlin, Div Thorac Surg, I-20122 Milan, Italy

[4] Univ Milan, Dept Pathophysiol & Organ Transplantat, I-20122 Milan, Italy

[5] San Gerardo Hosp, Dept Pathol, I-20900 Monza, Italy

[6] San Gerardo Hosp, Dept Surg, I-20900 Monza, Italy

[7] Milano Bicocca Univ, Sch Med & Surg, I-20900 Monza, Italy

[8] Osped San Paolo, UO Chirurg Epatobiliopancreat & Digest, I-20142 Milan, Italy

[9] Univ Milan, Dept Hlth Sci, I-20122 Milan, Italy

[10] Radboud Univ Nijmegen, Fac Sci, Dept Mol Biol, Nijmegen, Netherlands

[11] Univ Milan, Dept Clin Sci & Community Hlth, I-20122 Milan, Italy

[12] Univ Milan, Dept Med Biotechnol & Translat Med, I-20129 Milan, Italy

来源：

IMMUNITY | 2016年 / 45卷 / 05期

基金：

欧洲研究理事会;

关键词：

IMMUNE CHECKPOINTS; ANTITUMOR-ACTIVITY; TREG CELLS; CANCER; BLOCKADE; EFFECTOR; CCL18; DIFFERENTIATION; METASTASIS; MECHANISMS;

D O I：

10.1016/j.immuni.2016.10.021

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deepermolecular 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.

引用

页码：1135 / 1147

页数：13

共 55 条

[1]

A Distinct Function of Regulatory T Cells in Tissue Protection [J].

Arpaia, Nicholas ;

Green, Jesse A. ;

Moltedo, Bruno ;

Arvey, Aaron ;

Hemmers, Saskia ;

Yuan, Shaopeng ;

Treuting, Piper M. ;

Rudensky, Alexander Y. .

CELL, 2015, 162 (05) :1078-1089

[2]

Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer [J].

Bindea, Gabriela ;

Mlecnik, Bernhard ;

Tosolini, Marie ;

Kirilovsky, Amos ;

Waldner, Maximilian ;

Obenauf, Anna C. ;

Angell, Helen ;

Fredriksen, Tessa ;

Lafontaine, Lucie ;

Berger, Anne ;

Bruneval, Patrick ;

Fridman, Wolf Herman ;

Becker, Christoph ;

Pages, Franck ;

Speicher, Michael R. ;

Trajanoski, Zlatko ;

Galon, Jerome .

IMMUNITY, 2013, 39 (04) :782-795

[3]

CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data [J].

Bindea, Gabriela ;

Galon, Jerome ;

Mlecnik, Bernhard .

BIOINFORMATICS, 2013, 29 (05) :661-663

[4]

Layilin, a novel talin-binding transmembrane protein homologous with C-type lectins, is localized in membrane ruffles [J].

Borowsky, ML ;

Hynes, RO .

JOURNAL OF CELL BIOLOGY, 1998, 143 (02) :429-442

[5]

Biochemical Signaling of PD-1 on T Cells and Its Functional Implications [J].

Boussiotis, Vassiliki A. ;

Chatterjee, Pranam ;

Li, Lequn .

CANCER JOURNAL, 2014, 20 (04) :265-271

[6]

A Special Population of Regulatory T Cells Potentiates Muscle Repair [J].

Burzyn, Dalia ;

Kuswanto, Wilson ;

Kolodin, Dmitriy ;

Shadrach, Jennifer L. ;

Cerletti, Massimiliano ;

Jang, Young ;

Sefik, Esen ;

Tan, Tze Guan ;

Wagers, Amy J. ;

Benoist, Christophe ;

Mathis, Diane .

CELL, 2013, 155 (06) :1282-1295

[7]

Phenotypical and functional specialization of FOXP3+ regulatory T cells [J].

Campbell, Daniel J. ;

Koch, Meghan A. .

NATURE REVIEWS IMMUNOLOGY, 2011, 11 (02) :119-130

[8]

Preoperative CTLA-4 Blockade: Tolerability and Immune Monitoring in the Setting of a Presurgical Clinical Trial [J].

Carthon, Bradley C. ;

Wolchok, Jedd D. ;

Yuan, Jianda ;

Kamat, Ashish ;

Tang, Derek S. Ng ;

Sun, Jingjing ;

Ku, Geoffrey ;

Troncoso, Patricia ;

Logothetis, Christopher J. ;

Allison, James P. ;

Sharma, Padmanee .

CLINICAL CANCER RESEARCH, 2010, 16 (10) :2861-2871

[9]

CCL18 from Tumor-Associated Macrophages Promotes Breast Cancer Metastasis via PITPNM3 [J].

Chen, Jingqi ;

Yao, Yandan ;

Gong, Chang ;

Yu, Fengyan ;

Su, Shicheng ;

Chen, Jianing ;

Liu, Bodu ;

Deng, Hui ;

Wang, Fengsong ;

Lin, Ling ;

Yao, Herui ;

Su, Fengxi ;

Anderson, Karen S. ;

Liu, Qiang ;

Ewen, Mark E. ;

Yao, Xuebiao ;

Song, Erwei .

CANCER CELL, 2011, 19 (04) :541-555

[10]

PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells [J].

Cipolletta, Daniela ;

Feuerer, Markus ;

Li, Amy ;

Kamei, Nozomu ;

Lee, Jongsoon ;

Shoelson, Steven E. ;

Benoist, Christophe ;

Mathis, Diane .

NATURE, 2012, 486 (7404) :549-U151

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