CD4 and neoplasm: Cytotoxic T lymphocytes (CTLs), which are differentiated from CD8+ T cells and activated by antigen-presenting cells when faced with tumor cells, can directly kill tumor cells through releasing granules containing perforin, granzyme, and/or granulysin60,61, whereas CD4+ helper T cells (Th) secrete inflammatory factors such as IL-2, IL-4, IL-6, IFN-γ, etc., which can activate multiple immune cells (including CTLs, macrophages, B lymphocytes, and natural killer cells) to exert indirect anti-tumor effects and achieve tumor killing62,63.