The low efficacy of ICI alone for HER2-altered NSCLC might be attributed to three main mechanisms: (1) “cold phenotype” due to a low cytotoxic CD8+ T cell infiltration and PD-L1 expression; (2) low TMB, which could be associated with low tumour-specific antigens; (3) and a lack of co-mutations, which makes the tumour more sensitive to immunotherapy [109]. This evidence concerns the gene CD274 and neoplasm.