title: Patients with oral squamous cell carcinoma are characterized by increased frequency of suppressive regulatory T cells in the blood and tumor microenvironment.
abstract: Oral squamous cell carcinoma (OSCC) is a cancerous lesion with high incidence worldwide. The immunoregulatory events leading to OSCC persistence remain to be elucidated. Our hypothesis is that regulatory T cells (Tregs) are important to obstruct antitumor immune responses in patients with OSCC. In the present study, we investigated the frequency, phenotype, and activity of Tregs from blood and lesions of patients with OSCC. Our data showed that >80% of CD4(+)CD25(+) T cells isolated from PBMC and tumor sites express FoxP3. Also, these cells express surface Treg markers, such as GITR, CD45RO, CD69, LAP, CTLA-4, CCR4, and IL-10. Purified CD4(+)CD25(+) T cells exhibited stronger suppressive activity inhibiting allogeneic T-cell proliferation and IFN-gamma production when compared with CD4(+)CD25(+) T cells isolated from healthy individuals. Interestingly, approximately 25% of CD4(+)CD25(-) T cells of PBMC from patients also expressed FoxP3 and, although these cells weakly suppress allogeneic T cells proliferative response, they inhibited IFN-gamma and induced IL-10 and TGF-beta secretion in these co-cultures. Thus, our data show that Treg cells are present in OSCC lesions and PBMC, and these cells appear to suppress immune responses both systemically and in the tumor microenvironment.
authors.affiliation: Department of Biological Sciences, Bauru Dental School, University of São Paulo, Al. Octávio Pinheiro Brisolla, 9-75, CEP 17012-901, Bauru, SP, Brazil thaisgasparoto@usp.br
authors.forename: Thaís Helena
authors.initials: TH
authors.lastname: Gasparoto
authors.forename: Tatiana Salles
authors.initials: TS
authors.lastname: de Souza Malaspina
authors.forename: Luciana
authors.initials: L
authors.lastname: Benevides
authors.forename: Edgard Jose Franco
authors.initials: EJ
authors.lastname: de Melo
authors.forename: Maria Renata Sales Nogueira
authors.initials: MR
authors.lastname: Costa
authors.forename: José Humberto
authors.initials: JH
authors.lastname: Damante
authors.forename: Maura Rosane Valério
authors.initials: MR
authors.lastname: Ikoma
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
authors.forename: Karen Angélica
authors.initials: KA
authors.lastname: Cavassani
authors.forename: João Santana
authors.initials: JS
authors.lastname: da Silva
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Campanelli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019139:Tumor Escape
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors