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OX40, a member of the tumor necrosis factor receptor superfamily, is selectively expressed on activated T-cells. The engagement of OX40 during interactions between T-cells and dendritic cells is essential for the clonal expansion of antigen-specific T-cells and the establishment of T-cell memory. Recent animal model studies have highlighted the significant role of OX40 in the development of immunologic abnormalities, including inflammatory, autoimmune, infectious, allergic, and allotransplantation-related diseases. Inhibition of the OX40-OX40L interaction has demonstrated potential in preventing, curing, or alleviating these conditions. Conversely, OX40 activation can disrupt tolerance in cancer, reactivating antitumor immunity. These insights underscore the OX40/OX40L system as a promising target for immunotherapeutic interventions in the treatment of these diseases.