OX40-OX40L Axis in Cutaneous T-Cell Lymphomas: Pathogenic, Prognostic, and Potential Therapeutic Perspectives

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most prevalent forms of cutaneous T-cell lymphoma (CTCL) and are characterized by the proliferation of CD4⁺ T-helper cells. The pathogenesis of CTCLs involves a critical interaction between neoplastic cells and the tumor microenvironment. This interaction is driven not only by cytokines but also by surface proteins that mediate cell-cell contact. One such protein, OX40 (also known as CD134), is a member of the TNF receptor superfamily and serves as an induced costimulatory molecule that facilitates the interaction between T-cells and antigen-presenting cells. In this narrative review, we explore the literature surrounding the OX40-OX40L interaction in CTCLs, highlighting its pathogenic and prognostic significance. Additionally, we compare the expression and function of OX40-OX40L in chronic inflammatory skin diseases, such as atopic dermatitis and psoriasis, with their role in CTCLs. Finally, we provide an overview of the current state of therapeutic research, discussing the potential of targeting the OX40-OX40L axis in CTCL treatment.