Both for ICI as well as cell-based immunotherapies (adoptive tumor infiltrating lymphocyte (TIL) and chimeric antigen receptor T cell (CART cell)), no or negligible anti-tumor responses are observed, when CD8+ effector and CD4+ helper T cells are sparse or absent from the TME or if they are inactive due to immunosuppressive signaling in and by the tumor and TME [1–3]. This evidence concerns the gene CD4 and neoplasm.