Zander and colleagues identified a critical role for CD4+ T cell-derived interleukin (IL)-21 in driving the differentiation of a CX3CR1+ cytotoxic effector CD8+ T cell subtype with enhanced anti-viral and anti-tumour activity against murine B16F10 melanoma tumours (an immunologically-cold, aggressive tumour that is refractory to ICB therapy) [43]. The gene discussed is CD8A; the disease is melanoma.