In particular, in HNSCC, high levels of activated tumour-specific T cells are required to overcome the immune suppression induced by tumour mass, and the synergistic involvement of both CD8+CD137+ and CD4+CD137+ T cells is particularly important in this type of tumour, which is characteristic of a highly immunosuppressive milieu [29]. The gene discussed is TNFRSF9; the disease is head and neck squamous cell carcinoma.