Germ-free mice demonstrate a decrease in αβ T cells, CD4+ and CD8+T cells, Th1 cells, Th17 cells, CD4+CD25+ T cells, γδ T cells, and antibody-secreting plasma cells in various parts of the body including intestine, spleen, lymph nodes and in the circulation when compared to specific pathogen-free mice, and demonstrate reduced expression of Angiogenin-4, regIIIγ, secretory IgA, TLR9, MHC class II, and IL25 at the intestinal cells [63,195], resulting in poor anti-cancer protection by the immune system. This evidence concerns the gene CD4 and cancer.