The combination therapies involving these novel ICs – whether in conjunction with PD-1/PD-L1 and CTLA-4, or in collaboration with nanomaterials, oncolytic viruses (OVs) and tumour vaccines – have ignited a wave of research enthusiasm, offering new hope for immunotherapy in HNSCC. The gene discussed is CTLA4; the disease is head and neck squamous cell carcinoma.