CD28 and neoplasm: demonstrated that mutating the PYAPP of CD28 to AYAAA eliminated the ability of PYAP to bind to LCK to eliminate IL-2-induced signaling, reduced the promotion of IL-2 to intratumor regulatory T cell (Treg), and achieved enhanced function of CD28-based CAR-T cells by decreasing the solid Treg cell infiltration in the tumor to achieve the functional enhancement of CD28-based CAR-T, which significantly improved the anti-tumor activity of solid tumors with a large number of Treg infiltration (54).