OX40 is a member of the TNF receptor family, which is mainly known to promote effector T cell differentiation, proliferation, long-term survival, and pro-infammatory cytokines production, while inhibiting differentiation and suppressive activity of regulatory T cells (Tregs). It is expressed on activated CD4+ and CD8+ T cells, as well as on other cell types. The OX40 ligand, expressed by antigen presenting cells (APC), activates the OX40 signaling pathway which promotes a robust immune response. The interaction of OX40 with OX40 ligand results in enhanced CD4+ and CD8+ cell proliferation, stimulated cytokine production, and increased survival of antigen specific memory T cell. OX40 expression was revealed as an unfavorable prognostic marker and might be a target for immunotherapy in the future. OX40 was identified as a novel molecule in EC; its elevated expression tends to signify favorable clinical outcomes. As a second immune checkpoint, OX40 may have potential implications for the prognosis and immunomodulation of EC patients. In mice, the absence of OX40 has been shown to cause a strong reduction in the number of effector memory CD4+ cells. Furthermore, the CD8+ response was reduced and tumor growth was accelerated. Accordingly, it is comprehensible that the immune-stimulating properties of OX40 agonists could overcome some of the immunosuppressive properties within tumor environment.