Decreased levels of alternative co-stimulatory receptors OX40 and 4-1BB characterise T cells from head and neck cancer patients

BACKGROUND AND AIM: Head and neck cancers (HNC) are aggressive tumours. Tumour-specific T cells are frequently identified in patients with cancer, although they fail to control tumour progression. A family of proteins called co-stimulatory receptors regulate the function of T cells and may account for T cell dysfunction in cancer. Our aim was to characterise co-stimulatory receptors on T cells in HNC patients to identify novel targets for immunotherapy.

METHODS: Peripheral blood mononuclear cells were isolated from HNC patients and healthy controls and the expression of co-stimulatory (OX40, 4-1BB, ICOS) and co-inhibitory (CTLA-4, PD1) receptors was analysed on CD4(+) and CD8(+) T cells using flow cytometry.

RESULTS: We found that the levels of co-stimulatory receptors OX40 and 4-1BB were significantly lower on CD4(+) T cells from HNC patients. This was more pronounced in locally advanced tumours (T3/T4) compared to early carcinomas (T1/T2). PD-1 levels were higher on CD8(+) T cells in HNC patients compared to controls. Human papilloma virus (HPV)-specific CD8(+) T cells appeared to be more affected than Influenza-specific T cells.

CONCLUSIONS: Our results indicate that expression of co-stimulatory receptors on T cells from HNC patients is imbalanced with a preponderance of inhibitory signals, and reduction of stimulatory signals, especially in advanced disease. Restoring this balance could improve T cell therapy outcomes in HNC.