Most insights into the differentiation and functional requirements of cytotoxic CD4+ T cells are in the context of viral immunity, which may not involve similar cues to those of cancer; even with the viral context, it is noteworthy that the efficiency of cytotoxic CD4+ T cell generation is itself dependent on the specific viral context (e.g., retroviral versus adenoviral; Donnarumma et al., 2016). This evidence concerns the gene CD4 and cancer.