ABSTRACT
BACKGROUND AND OBJECTIVES: OX40, a membrane-bound molecule of the tumor-necrosis-factor-receptor superfamily, is a critical costimulatory receptor during the immune response, especially to T cells, but studies described their presence of OX-40 on neutrophils and monocytes, suggesting a potential role in the activation of immune response. Our aim was to characterize costimulatory receptors OX40 expression on circulating leukocytes in gastric cancer to identify novel targets for immunotherapy. METHODS: Peripheral blood mononuclear cells were isolated from 24 gastric cancer patients and 34 healthy controls and the expression of costimulatory (OX40) receptors were analyzed on T cells, neutrophil and monocyte using monoclonal antibodies by flow cytometry. RESULTS: We found that the higher levels of OX40 + T cells, monocytes/OX40+ and neutrophils/OX40+ from gastric cancer patients when compared to controls (P < 0.0001), and also higher levels of OX40+ T cells when compared to stages III and IV (P = 0.02). Percentage levels of total T cells were similar between patients and controls. CONCLUSIONS: OX40 as a therapeutic agent has been investigated in many preclinical tumor models. Our findings suggest that of levels of costimulatory in T cells in GC will direct future studies on the role that costimulatory receptors play in the failure of T cell-mediated immunity.
Subject(s)
Antibodies, Monoclonal/immunology , Leukocytes, Mononuclear/immunology , Monocytes/immunology , Receptors, OX40/immunology , Stomach Neoplasms/immunology , T-Lymphocytes/immunology , Case-Control Studies , Female , Follow-Up Studies , Humans , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/pathology , Male , Middle Aged , Monocytes/metabolism , Monocytes/pathology , Prognosis , Receptors, OX40/agonists , Receptors, OX40/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , T-Lymphocytes/metabolism , T-Lymphocytes/pathologySubject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Mutational Analysis , Germ-Line Mutation , Immunohistochemistry , Mismatch Repair Endonuclease PMS2/genetics , MutL Protein Homolog 1/genetics , Biomarkers, Tumor/metabolism , Colorectal Neoplasms, Hereditary Nonpolyposis/enzymology , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Humans , Mismatch Repair Endonuclease PMS2/metabolism , Phenotype , Predictive Value of TestsABSTRACT
Objectives: This study aimed to evaluate the expression pattern of some markers (E-cadherin and â-catenin) related to cellular adhesion and their relationship with histological tumor type according to Lauréns system, clinicopathological features and patient survival. Material and Methods: We did immunohistochemical analysis in a retrospective series of 446 gastric carcinomas using tissue microarray method (TMA). Clinicopathological features and overall survival data of all patients were retrospectively reviewed from hospital records. For all statistical analyses, p<0.05 was considered significant. Results: The reduced/absent expression of E-cadherin occurred more frequently in diffuse than intestinal type tumors and it was correlated with worse biological behavior and poor prognosis for patients with diffuse type gastric carcinomas. The pattern of â-catenin expression was closely related to histological type and E-cadherin expression. Although patients with nuclear/absent â-catenin immunoreactivity showed worse survival index, no statistical correlation was found with overall survival. In multivariated analysis, only pTNM staging system persisted as independent prognostic marker. Conclusion: In the present study, alterations in E-cadherin/â-catenin complex expression showed significant correlations with clinicopathological parameters, as well as its implications for tumor progression and prognosis in gastric cancer. Our results indicate that markers expression pattern may be a useful marker of differentiation and suggest further investigations of their prognostic relevance to specific histological groups.
