OX40 transcriptomic expression and its association with immune checkpoints and clinical outcomes

Background: Preclinical data suggests a potential role for OX40 agonists in cancer treatment, though clinical trials have yielded modest results. Objectives: We assessed OX40 and other immune checkpoint RNA expression in advanced solid malignancies and their clinical outcomes. Design: We conducted a retrospective cohort study analyzing tissue samples from 514 cancer patients. Methods: Immune marker transcripts were evaluated using a clinical-grade laboratory test. OX40 expression was normalized, and percentiles ranked as "moderate/low" (0-74) or "high" (75-100). Results: High OX40 expression was found in 24% of tumors, primarily in esophageal, liver/bile duct, stomach, small intestine, and lung cancers. High OX40 was associated with increased expression of programmed death-1, cytotoxic T-lymphocyte-associated antigen-4, and forkhead box P3 but did not predict overall survival in immunotherapy-naïve patients or outcomes post-immunotherapy. Conclusion: OX40 expression is heterogeneous and strongly associated with immunosuppressive checkpoints, potentially suggesting that effective use of OX40 agonists may depend on patient selection based on tumor immunomics.