CD134

CD134, also known as OX40, is a cell surface receptor of the tumor necrosis factor receptor (TNFR) superfamily (TNFRSF4). It is primarily expressed on activated T cells, including CD4+ helper and CD8+ cytotoxic T cells, with surface levels increasing after antigen encounter. The receptor's ligand, OX40L (TNFSF4), is expressed on antigen-presenting cells such as dendritic cells, B cells, and macrophages, enabling ligand-receptor interaction during T cell activation.

When engaged by its ligand, OX40 transmits a potent costimulatory signal that enhances T cell proliferation, cytokine production (notably IL-2 and IFN-γ), survival, and the formation of memory T cells. The signaling cascade involves NF-κB, MAPK, and PI3K–AKT pathways, promoting sustained T cell responses. OX40 signaling can also modulate regulatory T cells, with context-dependent effects on immune suppression and tolerance.

Therapeutic interest centers on exploiting OX40 to boost anti-tumor immunity. OX40 agonists, including monoclonal antibodies and receptor-ligand fusion proteins, have been evaluated in preclinical studies and clinical trials, often in combination with PD-1/PD-L1 or CTLA-4 inhibitors. Results have shown potential enhancement of tumor control in some settings, but responses vary and safety concerns, such as inflammatory toxicities, have been noted.

CD134 plays a role in immune regulation beyond cancer, including responses to infectious agents and vaccines, where it supports effector function and durable memory. Its expression pattern and signaling properties make it a target for immunomodulation, with ongoing research to define optimal therapeutic strategies and patient populations.