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.
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Simone
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Arrigoni
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Grazisa
authors.initials: G
authors.lastname: Rossetti
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Gruarin
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ranzani
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Politano
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Raoul J P
authors.initials: RJP
authors.lastname: Bonnal
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Provasi
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Sarnicola
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Panzeri
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Moro
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Crosti
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Mazzara
authors.affiliation: 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.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vaira
authors.affiliation: 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.
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
authors.affiliation: Division of Thoracic Surgery, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Palleschi
authors.affiliation: 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.
authors.forename: Luigi
authors.initials: L
authors.lastname: Santambrogio
authors.affiliation: Department of Pathology, San Gerardo Hospital, Monza 20900, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bovo
authors.affiliation: Department of Pathology, San Gerardo Hospital, Monza 20900, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Zucchini
authors.affiliation: Department of Surgery, San Gerardo Hospital, Monza 20900, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Totis
authors.affiliation: Department of Surgery, San Gerardo Hospital, Monza 20900, Italy; School of Medicine and Surgery, Milano-Bicocca University, Monza 20900 Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Gianotti
authors.affiliation: School of Medicine and Surgery, Milano-Bicocca University, Monza 20900 Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Cesana
authors.affiliation: School of Medicine and Surgery, Milano-Bicocca University, Monza 20900 Italy.
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Perego
authors.affiliation: UO Chirurgia Epatobiliopancreatica e Digestiva Ospedale San Paolo, Milan 20142, Italy.
authors.forename: Nirvana
authors.initials: N
authors.lastname: Maroni
authors.affiliation: UO Chirurgia Epatobiliopancreatica e Digestiva Ospedale San Paolo, Milan 20142, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pisani Ceretti
authors.affiliation: UO Chirurgia Epatobiliopancreatica e Digestiva Ospedale San Paolo, Milan 20142, Italy; Department of Health Sciences, Università degli Studi di Milano, Milano 20122, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Opocher
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Francesco
authors.affiliation: Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
authors.forename: Jens
authors.initials: J
authors.lastname: Geginat
authors.affiliation: Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen, The Netherlands.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.affiliation: 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.
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.affiliation: 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.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pagani
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000401:mortality; D002469:Cell Separation; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000401:mortality; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059467:Transcriptome