TNF and neoplasm: The effector mechanisms employed by CD4+ T cells largely fall into two categories: first, the production of broad-acting soluble factors, such as IFN-γ and TNF-α, that promote an antiviral state in surrounding tissue,49 and second, direct cytotoxic activity.50, 51, 52 In the context of CD19-targeted CAR T cell therapy, CAR4 T cells directly engage and kill tumor cells in vitro to the same extent as CAR8 T cells, but they exhibit slower kinetics of cytotoxicity.53