Therapeutic advances in medical oncology · 2026
OX40 transcriptomic expression and its association with immune checkpoints and clinical outcomes.
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Thapa Bicky, Nishizaki Daisuke, Miyashita Hirotaka, Lee Suzanna, Nesline Mary K, Previs Rebecca A, Conroy Jeffrey M, Jensen Taylor J, DePietro Paul, Pabla Sarabjot, Kato Shumei, Kurzrock Razelle
Аннотация
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.
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.