Immune dysfunction in HNSCC has been extensively reported.3 The ICB that blocks cytotoxic T lymphocyte-associated protein 4 (e.g., ipilimumab) or PD1 (e.g., nivolumab and pembrolizumab) release the inhibitory cues imposed by tumour-derived signals and enable T cells to resume their immune activities.45 However, only a small proportion of patients (~ 15%) with R/M-HNSCC achieved durable remissions and prolonged survival.46 Thus, it is unclear why most of the patients do not respond to PD1/PDL1-targeted therapies. The gene discussed is CTLA4; the disease is head and neck squamous cell carcinoma.