TNF and neoplasm: They revealed that CAR-T cells showed high polyfunctionality in antitumor effector and stimulatory functions.22 In 2019, Xhangolli et al. demonstrated that CAR-T-cell activation involved a mixed T helper 1/2 cell response independent of differentiation in vitro.108 In their studies, both CD4 and CD8 CAR-T cells were equally effective in directly killing target tumor cells in vitro, and cytotoxic activity was associated with elevated coproduction of a wide range of cytokines (IFN-γ, TNF-α, GM-CSF, IL-5, IL-8, and IL-13).