The discovery of stem-like progenitor CD8+ Tex (Tpex) cells, the main responder to immune checkpoint blockade (ICB), attracts a large attention in both preclinical and clinical research field for developing next-generation cancer immunotherapies.322,324 In this section, we will summarize current understandings of the cellular and functional features of CD8+ and CD4+ T cells in chronic infection and tumor, their developmental pathways, regulatory mechanisms, CD4+ T cell help for CD8+ CTL responses, as well as contributions to anti-tumor immunity and checkpoint blockade. The gene discussed is CD4; the disease is cancer.