Avaliação do perfil de expressão dos mediadores solúveis PD-1, PD-L1, PD-L2, TIM-3, GAL-9, GITR e GITRL em pacientes com câncer gástrico

• Ano de defesa: 2025
• Autor(a) principal: Silva, Luciana Mata da [UNIFESP]
• Orientador(a): Forones, Nora Manoukian [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/48912/001300002g8cq
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo
• Palavras-chave em Português: Câncer gástrico; Biomarcadores tumorais; Inibidores de checkpoint imunológico; Moléculas estimuladoras do checkpoint; Neoplasias gástricas; Carcinogênese
• Palavras-chave em Inglês: Gastric cancer; Biomarkers tumor; Immune checkpoint proteins; Carcinogenesis; Stomach neoplasms
• Link de acesso: https://hdl.handle.net/11600/73988

Introduction: Cancer cells can present immune prevention or stimulation to regulate tumor progression and metastasis. PD-1, PD-L1, PD-L2, TIM-3, Gal9, GITR, and GITRL are immune checkpoints and are currently being evaluated as targets to modulate the antitumor immune response. The aim of this study was to evaluate the expression level of soluble sPD-1, sPD-L1, sPD-L2, sTIM-3, sGal9, sGITR, and sGITRL and determine their potential as biomarkers in the prognosis of gastric cancer (GC). Method: A cross-sectional and translational study was carried out at the Hospital de Cancer de Pernambuco and the Translational Research Laboratory of the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) between 2016 and 2019. A total of 74 patients with GC, without previous treatment, and 30 height controls were evaluated. Plasma sPD-1, sPD-L1, sPD-L2, sTIM-3, sGal9, sGITR, and sGITRL levels were measured by enzyme-linked immunosorbent assay (ELISA) before surgery. Results: We observed elevated serum levels of sPDL1 (p=0.0042), sTIM-3 (p=0.0072), sGITR (p=0.0179) and sGITRL (p=0.0055) in GC patients compared to height controls and low levels of sPD-1 (p=0.0179), sPDL2 (p=0.0003) and sGal9 (p<0.0001). We observed reduced levels of sGITR in GC patients who died in the first 24 months compared to those who survived (p=0.0332). We identified higher serum levels of sPD-1, sTIM-3 and sGal9 in patients with stage IV compared to stages I/II and III. Higher concentrations of sPD-L1, sGal9 and sGITRL in tumors found in the esophagogastric reserve when compared to tumors found in the body (p = 0.0303, p = 0.0025, p = 0.0003, respectively) and in the gastric antrum (p = 0.0091 and p = 0.0004, p = 0.0002, respectively). Smokers (p = 0.0109) and alcoholics (p = 0.0006) presented reduced serum concentrations of sGITRL. We did not find any statistically significant manifestation when we compared the serum concentrations of the mediators according to gender, histological type, angiolymphatic invasion, tumor size, lymph node involvement and degree of differentiation. Conclusion: It is concluded that there is an association of the levels of PD-1, TIM-3, Gal9 and GITR molecules with disease progression and/or death. This suggests that these molecules may be potential prognostic biomarkers in GC.