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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.
Therapeutic Advances in Medical Oncology
|July 15, 2026
Summary
High OX40 expression in tumors correlates with immune checkpoints but doesn't predict survival. Effective OX40 agonist therapy may require patient selection based on tumor immunomics.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Preclinical studies indicate OX40 agonists show promise for cancer treatment.
- Clinical trials using OX40 agonists have produced limited positive outcomes.
Purpose of the Study:
- To investigate OX40 and immune checkpoint RNA expression in advanced solid tumors.
- To correlate immune marker expression with clinical outcomes in cancer patients.
Main Methods:
- Retrospective cohort study of 514 cancer patients.
- Analysis of immune marker transcripts using a clinical-grade laboratory test.
- Categorization of OX40 expression as "moderate/low" or "high" based on normalized transcript levels.
Main Results:
- High OX40 expression was observed in 24% of tumors, notably in esophageal, liver/bile duct, stomach, small intestine, and lung cancers.
- Elevated OX40 expression was linked to increased programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and forkhead box P3 (FOXP3) expression.
- High OX40 expression did not predict overall survival in immunotherapy-naïve patients or outcomes following immunotherapy.
Conclusions:
- OX40 expression in tumors is heterogeneous.
- OX40 expression is significantly associated with immunosuppressive checkpoints like PD-1, CTLA-4, and FOXP3.
- Optimizing OX40 agonist therapy may necessitate patient stratification using tumor immunomics data.