Mounting evidence suggests a connection between acquisition of CSC characteristics and immunotherapy resistance in multiple carcinoma types including HNSCC.40 Indeed, targeting CSCs, such as inhibiting BMI1, and CD276, is effective in improving immunotherapy efficacy, suggesting that CSCs may be responsible for immune evasion in HNSCC.5,6,29 As expected, we found that patients with low LIMP-2 expression were prone to benefit from ICI therapy and further validated this finding with in vivo experiments, which may be related to the function of LIMP-2 to maintain CSC-like properties. The gene discussed is CD276; the disease is head and neck squamous cell carcinoma.