Given the pivotal role of the pleiotropic cytokine IL-21 in regulating CD8+ T cell effector function and naive CD4+ T helper (Th) cell polarization, we engineered 4/21 ICR-CAR–T cells in the presence of IL-4, resulting in their differentiation into a Th17-like phenotype and subsequent rapid tumor eradication [185]. This evidence concerns the gene CD8A and neoplasm.