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OX40 transcriptomic expression and its association with immune checkpoints and clinical outcomes
Bicky Thapa1, Daisuke Nishizaki2, Hirotaka Miyashita3
1Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215-5450, USA Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
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.