Neoantigens arisen from mutated proteins in cancer cells are cancer-specific and can be highly immunogenic. However, outgrowth of tumor clones down-regulating their antigens can evade from immune responses. Here, I defined constitutive neoantigen and facultative neoantigen according to the essentiality of neoantigen-expressing genes for tumor growth based on functional screening and single-cell transcriptome data. Our own and public cohort data revealed the influence of the gene-level properties on clinical responses to immune checkpoint inhibitor. The pre-therapy constitutive neoantigen load and on-therapy down-regulation of the constitutive neoantigens contributed to positive clinical responses. In contrast, patients with negative clinical responses showed expansion of tumor clones down-regulating facultative neoantigens, implying immunoediting. Therefore, immunoediting may possibly be minimized by steering anti-tumor immune responses toward neoantigens expressed from essential genes.