Chimeric antigen receptor T cell therapy: Revolutionizing cancer treatment

Figure 4 Chimeric antigen receptor T-mediated tumor cytotoxicity through three apoptotic pathways. A: Perforin-granzyme degranulation pathway: Chimeric antigen receptor (CAR) T cells recognize antigen-positive tumor cells through CAR-tumor-associated antigen binding, resulting in perforin and granzyme release driven targeted cell death; B: Cytokine-Mediated Pathway: Cytokine (e.g., interferon-gamma) secretion (here, due to the secondary cytokine transgene expression after nuclear factor of activated T cells-included CAR activation) sensitizes the stromal cells in the tumor microenvironment (TME). It upregulates complementary receptor expression and proper stromal targeting through ligand-receptor engagement; C: Death receptor-ligand [Fas/Fas ligand (FasL) Pathway: Antigen loss of tumor cells inside TME can be targeted using the death receptor-ligand engagement, through the formation of the FasL-receptor complex. CAR: Chimeric antigen receptor; IFN-γ: Interferon-gamma; NFAT: Nuclear factor of activated T cells; FasL: Fas ligand.