The article reviews the role of OX40 and its ligand OX40L in immune regulation and their potential as therapeutic targets in cancer. OX40, a member of the tumor necrosis factor receptor superfamily, is expressed on activated T cells and interacts with OX40L on antigen-presenting cells to enhance T-cell activation, proliferation, and survival. The interaction between OX40 and OX40L is crucial for immunoregulation, and its dysregulation can contribute to immune evasion in various cancers. Preclinical studies have shown that targeting OX40 with agonists can enhance anti-tumor immunity, but clinical trials have demonstrated limited efficacy, with responses observed in only a minority of patients. The expression patterns of OX40 and OX40L vary across different cancers, with a high percentage of patients showing high OX40 and low OX40L expression, which may be more amenable to OX40 agonist therapy. The article highlights the need for further research to identify biomarkers that can guide patient selection for OX40-based therapies and to optimize combination therapies with other immunotherapy agents.The article reviews the role of OX40 and its ligand OX40L in immune regulation and their potential as therapeutic targets in cancer. OX40, a member of the tumor necrosis factor receptor superfamily, is expressed on activated T cells and interacts with OX40L on antigen-presenting cells to enhance T-cell activation, proliferation, and survival. The interaction between OX40 and OX40L is crucial for immunoregulation, and its dysregulation can contribute to immune evasion in various cancers. Preclinical studies have shown that targeting OX40 with agonists can enhance anti-tumor immunity, but clinical trials have demonstrated limited efficacy, with responses observed in only a minority of patients. The expression patterns of OX40 and OX40L vary across different cancers, with a high percentage of patients showing high OX40 and low OX40L expression, which may be more amenable to OX40 agonist therapy. The article highlights the need for further research to identify biomarkers that can guide patient selection for OX40-based therapies and to optimize combination therapies with other immunotherapy agents.