COSTIMULATORY MOLECULE OX40, TUMOR IMMUNE MICROENVIRONMENT AND RESPONSE TO IMMUNOCHEMOTHERAPY IN DIFFUSE LARGE B‐CELL LYMPHOMA: AN INTEGRATIVE ANALYSIS WITH MOLECULAR CHARACTERISTICS

Background: OX40 is a crucial T-cell costimulatory molecule, but its molecular characteristics remain unclear in diffuse large B-cell lymphoma (DLBCL). Methods: We performed an integrative analysis of gene expression, somatic mutations and multiplex immunofluorescence to characterize the features, tumor immune microenvironment (TiME) clinical outcomes. Results: first identified that abnormally higher expression existed DLBCL than other cancers from discovery cohort, which was validated two independent cohorts. Then, we found elevated promoted patients have superior response immunochemotherapy via activating another cohort validation cohort. Elevated drove recruitment abundant infiltrating lymphocytes, leading stromal-immune score TiME, positively corrected with immune-related genes, including PD-1, CTLA4, TIGIT, VISTA, ICOS, GITR, 4-1BB CD28. Tumor mutational burden not mainly driver host responses mediated by OX40, BIRC6, STAT6 TNFRSF14 mutations. In high exhibited lower Ann Arbor stage (p = 0.039) IPI 0.047), were easier achieve CR/PR, especially both OX40L longer OS 0.008) PFS 0.010). infiltrated subsets analysis, greater number CD4+/OX40+ or CD8+/OX40+ T-cells had 0.021; p 0.009), while also maintained prognostic value for survival (HR 0.517; CI 0.276-0.968; 0.039). Conclusions: Overall, our findings provide insights application targeting combined agonists first-line patients. The research funded by: Natural Science Foundation Tianjin grants (19JCYBJC26500), Clinical Oncology Research Fund CSCO (Y-XD2019-162, Y-Roche20192-0097). Keywords: Basic Translational - Other, Aggressive non-Hodgkin No conflicts interests pertinent abstract.