Consistent with the well-defined role of CD40L in transmitting CD4 help for CD8+ T cells [75–77], it has been shown in different animal models that activated CD4+ T cells can license DCs in the tumor microenvironment via CD40L-CD40 interaction, leading to priming of tumor-reactive CD8+ T cells which in turn mediate long-term protection [78, 79]. The gene discussed is CD4; the disease is neoplasm.