CD4+ T cell subpopulations that play a critical role in immunotherapy include CD4+ Th1 cells that generate functional CD8+ T cell responses, CD4+FoxP3+ regulatory T cells (Treg) generally associated with suppression of antitumor immune responses in several cancers although responses to CTLA-4 blockade have been shown, and CD4+FoxP3−PD-1Hi (4PD-1Hi) T cells can indicate a negative prognosis when there is persistence after PD-1 blockade (6). This evidence concerns the gene CD4 and cancer.