Cell intrinsic PD-1 checkpoint blockade releases the brake on human chimeric antigen receptor (CAR) T cells for solid tumors

The immune system plays an important role in controlling and eliminating cancer. Nevertheless, tumors often evade endogenous immune responses due to tolerogenic mechanisms which prevent the rejection of malignant cells that are recognized as ‘self’ or alternatively, not ‘dangerous.’ The complex network of biological pathways that maintain tolerance involves several mediators, including myeloid and lymphoid-derived regulatory cells, immunosuppressive cytokines and chemokines, as well as immune checkpoint molecules that down-modulate anti-tumor immunity. The programmed cell death protein 1 (PD-1)—PD-1 ligand 1 (PD-L1) receptor-ligand pair is a principal immune checkpoint axis operative in the tumor microenvironment that attenuates T cell receptor (TCR)-mediated activation, leading to inhibition of T cell expansion and cytokine production (1-3).