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Overexpression of immunomodulatory mediators in oral precancerous lesions
Authors:Andréia Souza Gonçalves  Carla Mosconi  Filipe Jaeger  Isabela Jubé Wastowski  Maria Cássia Ferreira Aguiar  Tarcília Aparecida Silva  Rejane Faria Ribeiro-Rotta  Nádia Lago Costa  Aline Carvalho Batista
Institution:1. Department of Stomatology (Oral Pathology), Dental School, Federal University of Goiás, Goiânia, Brazil;2. Department of Oral Surgery and Pathology, Dental School, Federal University of Minas Gerais, Belo Horizonte, Brazil;3. Department of Biology, State University of Goiás, Morrinhos, Goiás, Brazil;4. Department of Stomatology (Oral Medicine), Dental School, Federal University of Goiás, Goiânia, Brazil
Abstract:Human leukocyte antigen (HLA) G and E, programmed cell death 1 ligand 1 (PD-L1), IL-10 and TGF-β are proteins involved in failure of the antitumor immune response. We investigated the expression of these immunomodulatory mediators in oral precancerous lesions (oral leukoplakia-OL; n = 80) and whether these molecules were related to the risk of malignant transformation. Samples of normal mucosa (n = 20) and oral squamous cells carcinoma (OSCC, n = 20) were included as controls. Tissue and saliva samples were analyzed by immunohistochemistry and ELISA respectively. Fifteen OL samples showed severe dysplasia (18.7%) and 40 samples (50%) presented combined high Ki-67/p53. Irrespective of the degree of epithelial dysplasia and the proliferation/apoptosis index of OL, the expression of HLA-G, -E, PD-L1, IL-10, TGF-β2 and -β3 was higher to control (P < 0.05) and similar to OSCC (P > 0.05). The number of granzyme B+ cells in OL was similar to control (P = 0.28) and lower compared to OSCC (P < 0.01). Salivary concentrations of sHLA-G, IL-10 and TGF-β did not allow for a distinction between OL and healthy individuals. Overexpression of immunosuppressive mediators in the OL reflects the immune evasion potential of this lesion, which is apparently independent of at cytological and proliferation/apoptosis status.
Keywords:HLA-G  human leukocyte antigen G  HLA-E  human leukocyte antigen E  PD-L1  programmed cell death 1 ligand 1  IL-10  interleukin-10  TGF-β  transforming growth factor beta  sHLA-G  soluble HLA-G  OL  oral leukoplakia  GB  granzyme B  OPL  oral precancerous lesions  CTLs  cytotoxic T lymphocytes  NK  natural killer  MHC  human major histocompatibility complex  PD-1  programmed cell death-1  OSCC  oral squamous cell carcinoma  SCC  squamous cell carcinoma  WHO  World Health Organization  IHC  immunohistochemistry  ELISA  enzyme-linked immunosorbent assay  UFG  Federal Universities of Goiás  UFMG  Federal Universities of Minas Gerais  H&E  hematoxylin-eosin  IRS  immunoreactive score  IQR  interquartile range  SPSS  Statistical Package for the Social Sciences  Oral leucoplakia  Immune evasion  HLA-G  Programmed cell death 1 ligand 1  Oral cancer
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