High soluble OX40 levels correlate with metastatic gastric cancer.

BACKGROUND AND OBJECTIVES: Previous studies demonstrated an association between OX40+T cell expression with poor prognosis in gastric cancer (GC). The soluble form of OX40 (sOX40) could block the interactions between OX40 on the effector T cell, and it is a ligand (OX40L) in dendritic cells. However, the role of sOX40 as a pretreating biomarker and prognostic predictor remains unclear. This study aimed to evaluate the association of levels of sOX40 and sOX40L with disease progression in GC. METHODS: Between 2017 and 2018, a cross-sectional study was performed on 83 GC patients and 20 healthy controls. RESULTS: Among 83 GC patients (median of 63 years), 32.4% of patients with I/II stages, 42.3% III, and 25.3% in IV stages. Metastatic GC patients had significantly higher levels of soluble OX40 compared with stage III (p = 0.0003) and early stages I and II patients (p = 0.005). There was no significant differences in the sOX40 and sOX40L levels between Lauren's histological subtype (intestinal, diffuse, and mixed). CONCLUSIONS: This study showed that soluble OX40 levels have an essential role in GC progression. OX40 molecules may constitute a predictor for poor prognosis and a potential target for immunotherapy in GC.

Unbalanced expression of sICOS and sPD-1 correlates with tumor progression in gastric cancer.

BACKGROUND AND OBJECTIVES: T cells are central in antitumor immunity in gastric cancer (GC). The inducible costimulatory molecule (ICOS) is a T cell receptor that primarily transmits positive signals for T cell activation and is associated with poor prognosis in GC. In contrast, the costimulatory molecule programmed death 1 (PD-1) is an inhibitory receptor related to tumor immune escape. This study aimed to analyze soluble sites and sPD-1 levels in GC. METHODS: This study enrolled 83 GC patients and 20 healthy controls. RESULTS: The median survival time was 23.22 months in the GC patients. Low levels of sPD-1 and sICOS in GC patients compared to the control group (p = 0.003; p < 0.0001, respectively). High sPD-1 levels in stage IV patients compared to I/II and III stages groups (p = 0.008 and p = 0.0004, respectively). GC patients with stages I and II had higher levels of sICOS compared to III and IV stages (p = 0.0005 and p = 0.02, respectively). There were no significant differences in sPD-1 and sICOS levels between Lauren subtypes. CONCLUSION: These results suggest a predominance of inhibitory costimulatory signals in advanced stages of GC, facilitating tumor immune escape, as the opposite occurs in early stages, resulting in an effective antitumor T-cell-mediated immune response.

Evaluation of platelet activation marker expression and its correlation with tumorigenesis and tumor progression in patients with gastric cancer.

BACKGROUND AND OBJECTIVES: Gastric cancer (GC) remains responsible for over one million new cases in 2020. Activated platelets express the CD40 ligand (CD40L) and CD62P in the cytoplasmic membrane, and interaction with the vascular endothelium can induce the production of tumor growth factors and metastases. We aimed to characterize the soluble levels of sCD40L and sCD62P in GC patients. METHODS: A cross-sectional study was performed on 83 GC patients and 20 healthy controls. RESULTS: High levels of sCD40L were obtained in GC patients compared to healthy controls (p = 0.003) and in the I/II compared with III and IV stages (p < 0.0001 and p = 0.007, respectively). Low levels of sCD62P in the GC patients compared to healthy controls (p = 0.009). High soluble levels of sCD62P in I/II compared with III and IV stages (p = 0.002 and p = 0.01, respectively). There are no significant differences in the levels of sCD40L and sCD62P were observed between intestinal, diffuse, and mixed types. CONCLUSIONS: We concluded that sCD40L and sCD62P molecules may be predictive biomarkers since the increase in plasma levels was associated with disease progression and metastasis in GC. In addition, the serum sCD40L and sCD62P can potentially be used as an indicator of response to anticancer therapy.