CD4 and neoplasm: The precise molecular pathways that guide differentiation of tumor antigen-specific CD4 T cells into cytolytic effectors versus regulatory T cells are still poorly understood, but animal studies indicate that neoantigen expression leads to tumor regulatory T-cell accumulation [343], and a large proportion of immunologically active tumors contain actively proliferating Tregs alongside CD8 T cells and conventional, i.e., Foxp3-negative CD4 T cells.