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High soluble OX40 serum levels correlate with metastatic gastric adenocarcinoma
Interaction between membrane-bound molecule OX40, a member of the tumor necrosis factor receptor superfamily, and its ligand OX40L has an important role in T cell-mediated immune responses, which is the primary mechanism involved in immunity against cancer. Previous studies demonstrated an association between OX40/OX40L altered expression in T cell membranes and poor prognosis in gastric cancer (GC). It is hypothesized that the soluble form of OX40 (sOX40) in blood suppresses T cell activation by blocking the OX40/OX40L interaction, and therefore could also mediate antitumor immune responses and be a potential target for immunotherapy. However, the role of sOX40 as a pretreating biomarker and prognostic predictor remains unclear.
To examine the association between serum levels of sOX40 and soluble OX40L (sOX40L) and tumor progression in patients with GC.
Serum samples were collected from 83 patients with gastric adenocarcinoma, and OX40 e OX40L serum levels were quantified via enzyme-linked immunosorbent assay. Patients were stratified according to TNM staging.
Patients with stage IV metastatic gastric cancer had significantly higher levels of soluble OX40 in comparison with stage III patients with lymph nodes metastasis (median 60.7 pg/ml, 95% IC 25.66 pg/ml to 95.78 pg/ml, p value=0.0003) and early stages I and II patients (median 52.26 pg/ml, 95% IC 13.85 pg/ml to 90.66 pg/ml, p value=0.005). There was no statistically significant difference between early and advanced gastric cancer regarding serum levels of soluble OX40 ligand (sOX40L). Serum levels of sOX40 and sOx40L did not differ between gastric cancer histological subtypes.
This study successfully demonstrated a higher level of soluble OX40 in peripheral blood in patients with advanced gastric cancer compared with early stages and non metastatic disease. These results suggest that T cell activation costimulatory molecule sOX40 has an important role in gastric cancer progression, possibly due to the inhibition of antitumor immunity induced by sOX40. Serum levels of sOX40 correlate with advanced gastric cancer, and may constitute a predictor for poor prognosis, as well as a potential target for immunotherapy.
soluble OX40, gastric cancer, immunotherapy
Trato gastrointestinal alto*
CECÍLIA ARAÚJO CARNEIRO LIMA, MÁRIO RINO MARTINS, ROGÉRIO LUIZ DOS SANTOS, LUCIANA MATA DA SILVA, JERÔNIMO PAULO ASSIS DA SILVA, LEURIDAN CAVALCANTE TORRES, NORA MANOUKIAN FORONES