Role of OX40 and its ligand as costimulatory modulators in cancer immunotherapy

Abstract

Body‟s defence mechanism has ability to combat tumour cells but tumour cells can circumvent immune system in order to flourish. Therefore, current research focuses on reinvigorating immune system to combat against extensive range of human malignancies through immunotherapy. Recently, immuno-therapy has demonstrated beneficial outcomes in cancers treatment but the main drawbacks are primary and acquired resistance to the therapeutic agents and immune-related toxicities. Therefore, novel immune therapies are direly required. Co-stimulatory molecules such as TNF Receptor Superfamily Member 4 (OX40, CD134) and its ligand TNF Superfamily Member 4 (CD252, OX40L) are expressed on different immune cells. The mutual interaction between OX40 and its ligand (OX40/OX40L) decreases the functional capacity of immunosuppression offered by regulatory T cells (Tregs) and induces the proliferation of T cells against specific antigen enhancing the immune response. Many clinical trials are focusing on OX40/OX40L therapeutic agents to find out whether they have therapeutic effect on cancer treatment. The initial phase trials result of OX40 and its ligands focusing therapeutic agents are encouraging but still not sufficient. This review will concentrate on the cellular and molecular pathways of OX40-mediated T-cell co-stimulation, the expression of OX40 and OX40L in tumours, the implications of their interactions and their under-or over-expression patterns, with particular focus on the function of OX40 in tumours of different origins. Finally, we discuss results of clinical trials of OX40 and OX40L directed pharmacotherapy and the lacunae that need to be filled.