CD28 and neoplasm: Certain tumor-infiltrating T cells exhibit elevated PD-1 expression, and the interaction between PD-1 and PD-L1 can negate CD28 co-stimulation, thereby diminishing T cell responses, however, CD2-CD58 co-stimulatory signaling demonstrates reduced sensitivity to PD-1 inhibition, establishing it as a crucial co-stimulation-adhesion axis that facilitates an anti-tumor response (27).