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

doi:10.1016/j.immuni.2016.10.021

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

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

480 Citaten (Scopus)

Samenvatting

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.

Originele taal-2	Engels
Pagina's (van-tot)	1135-1147
Aantal pagina's	13
Tijdschrift	Immunity
Volume	45
Nummer van het tijdschrift	5
DOI's	https://doi.org/10.1016/j.immuni.2016.10.021
Status	Gepubliceerd - 15 nov. 2016
Extern gepubliceerd	Ja

Toegang tot document

10.1016/j.immuni.2016.10.021

Citeer dit

De Simone, M., Arrigoni, A., Rossetti, G., Gruarin, P., Ranzani, V., Politano, C., Bonnal, R. J. P., Provasi, E., Sarnicola, M. L., Panzeri, I., Moro, M., Crosti, M., Mazzara, S., Vaira, V., Bosari, S., Palleschi, A., Santambrogio, L., Bovo, G., Zucchini, N., ... Pagani, M. (2016). Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells. Immunity, 45(5), 1135-1147. https://doi.org/10.1016/j.immuni.2016.10.021

@article{986ad1c6aec241a3afd8203ca8d99f46,

title = "Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s)",

year = "2016",

month = nov,

day = "15",

doi = "10.1016/j.immuni.2016.10.021",

language = "English",

volume = "45",

pages = "1135--1147",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "5",

}

De Simone, M, Arrigoni, A, Rossetti, G, Gruarin, P, Ranzani, V, Politano, C, Bonnal, RJP, Provasi, E, Sarnicola, ML, Panzeri, I, Moro, M, Crosti, M, Mazzara, S, Vaira, V, Bosari, S, Palleschi, A, Santambrogio, L, Bovo, G, Zucchini, N, Totis, M, Gianotti, L, Cesana, G, Perego, RA, Maroni, N, Pisani Ceretti, A, Opocher, E, De Francesco, R, Geginat, J, Stunnenberg, HG, Abrignani, S & Pagani, M 2016, 'Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells', Immunity, vol. 45, nr. 5, blz. 1135-1147. https://doi.org/10.1016/j.immuni.2016.10.021

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

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 - http://www.scopus.com/inward/record.url?scp=84999673353&partnerID=8YFLogxK

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 -

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

Samenvatting

Toegang tot document

Vingerafdruk

Citeer dit