Such cytotoxic CD4+ T cells are found in both mice and humans in a wide range of pathological conditions (Juno et al., 2017), including murine cancer models where melanoma-reactive CD4+ T cells acquire cytotoxic activity and eliminate large transplantable and spontaneous mouse melanoma tumors (Quezada et al., 2010, Xie et al., 2010). Here, CD4 is linked to cancer.