OX40 signaling in head and neck squamous cell carcinoma: Overcoming immunosuppression in the tumor microenvironment

• Anti-OX40 is a promising antibody that is currently in early phase clinical trials for the treatment of cancer.
• OX40 is highly expressed in the tumor infiltrating lymphocytes of patients with head and neck squamous cell carcinoma.
• Preclinical models have suggested synergy between anti-OX40 and anti-PD1, anti-OX40 and anti-CTLA-4, as well as anti-OX40 and anti-PDL1.
• Anti-OX40 is currently being tested in early phase human clinical trials, both as monotherapy and in combination with other immunotherapies, in head and neck squamous cell carcinoma.

SummaryOX40 is a member of the tumor necrosis factor (TNF) receptor family and a potent co-stimulatory pathway that when triggered can enhance T-cell memory, proliferation and anti-tumor activity in patients with metastatic cancer. Ongoing investigations at our institution have demonstrated that OX40 expressing T cells are found in abundance in the tumors of patients with advanced stage head and neck squamous cell carcinoma (HNSCC). This has led to the initiation of human clinical trials investigating OX40-directed therapy for patients with HNSCC in both the metastatic and curative setting. The purpose of this review is to explore what is known about OX40 signaling and discuss how this pathway potentially can be modulated to improve outcome for patients with HNSCC.