title: Squamous Cell Tumors Recruit γδ T Cells Producing either IL17 or IFNγ Depending on the Tumor Stage.
abstract: The identification of reciprocal interactions between tumor-infiltrating immune cells and the microenviroment may help us understand mechanisms of tumor growth inhibition or progression. We have assessed the frequencies of tumor-infiltrating and circulating γδ T cells and regulatory T cells (Treg) from 47 patients with squamous cell carcinoma (SCC), to determine if they correlated with progression or survival. Vδ1 T cells infiltrated SSC tissue to a greater extent than normal skin, but SCC patients and healthy subjects had similar amounts circulating. However, Vδ2 T cells were present at higher frequencies in circulation than in the tissue of either cancer patients or healthy donors. Tregs were decreased in the peripheral blood of SCC patients, but were significantly increased in the tumor compartment of these patients. Tumor-infiltrating γδ T cells preferentially showed an effector memory phenotype and made either IL17 or IFNγ depending on the tumor stage, whereas circulating γδ T cells of SCC patients preferentially made IFNγ. Different cell types in the tumor microenvironment produced chemokines that could recruit circulating γδ T cells to the tumor site and other cytokines that could reprogram γδ T cells to produce IL17. These findings suggest the possibility that γδ T cells in SCC are recruited from the periphery and their features are then affected by the tumor microenvironment. Elevated frequencies of infiltrating Vδ2 T cells and Tregs differently correlated with early and advanced tumor stages, respectively. Our results provide insights into the functions of tumor-infiltrating γδ T cells and define potential tools for tumor immunotherapy.Cancer Immunol Res; 5(5); 397-407. ©2017 AACR.
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy.|Department of Biopathology and Medical Biotechnologies (DIBIMED), University of Palermo, Palermo, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Lo Presti
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Plastic and Reconstructive Surgery, University of Palermo, Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Toia
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Plastic and Reconstructive Surgery, University of Palermo, Palermo, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Oieni
authors.affiliation: Department for the Treatment and Study of Abdominal Diseases and Transplantation, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Buccheri
authors.affiliation: Department of Surgical and Oncological and Oral Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Turdo
authors.affiliation: Department of Surgical and Oncological and Oral Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy.
authors.forename: Laura Rosa
authors.initials: LR
authors.lastname: Mangiapane
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Campisi
authors.affiliation: Department of Dermatology, University of Palermo, Palermo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Caputo
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy.|Department of DIBIMIS, University of Palermo, Palermo, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Todaro
authors.affiliation: Department of Surgical and Oncological and Oral Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Stassi
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Plastic and Reconstructive Surgery, University of Palermo, Palermo, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cordova
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Plastic and Reconstructive Surgery, University of Palermo, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Moschella
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Gaetana
authors.initials: G
authors.lastname: Rinaldi
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy. serena.meraviglia@unipa.it.|Department of Biopathology and Medical Biotechnologies (DIBIMED), University of Palermo, Palermo, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Meraviglia
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy.|Department of Biopathology and Medical Biotechnologies (DIBIMED), University of Palermo, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D016207:Cytokines