Multiple studies mentioned that, except for the well-established role of tumor neoantigen-specific CD8+ T cells in antitumor immunity, HLA class II presenting neoantigens to CD4+ T cells also exerted a crucial function in tumor eradication and response to immunotherapy.58 78 79 Despite that, some cancer patients responded to immunotherapy even without detectable HLA class II,58 indicating that the mechanisms of HLA class II in immune regulation and antitumor immunity remain to be elaborated. This evidence concerns the gene CD4 and cancer.