Fig. 2

Antitumor mechanism of CAR-T. a TCR recognizes TAAs depending on the MHC presentation. The advantage is that TCR could recognize intracellular and extracellular antigens. While tumor cells often downregulate MHC expression to escape the killer T cells, b CAR-T cells can specifically recognize the tumor antigens in a MHC-independent manner. And then, the T cells were activated through the phosphorylation of ITAMs followed by enhanced cytokine (include IL-2, IL-4, IFN-γ, IL-12, and TNF) secretion, T cell proliferation, and cytotoxicity. IL-12 could recruit and reinforce the functions of innate immune cells such as NK cell and macrophage. Activated T and CAR-T cells perform cytotoxicity mainly through secretion of perforin and granzyme granules, also through the death receptor pathway such as Fas/Fas-L. Due to added co-stimulatory signal to endodomain, antitumor activity mediated by CARs is stronger than TCRs