The efficacy of PD-1/PD-L1 blockade in cold cancers and future perspectives

Abstract

Colorectal cancer (CRC), and breast, ovarian, pancreatic and prostate cancers are generally considered as low immune-reactive cancers that represent either limited infiltration of immune cells or extensive infiltration of immunosuppressive T cells. Interaction between programmed death ligand 1 (PD-L1) with programmed death-1 receptor (PD-1) is important for immune evasion. Tumors positive for PD-L1 generally show higher responses to the immune checkpoint inhibition (ICI); however, the high presence of PD-L1 in a tumor is a predictor of poor prognosis. Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, but responses to the ICI is meaningful. It seems that in a tumor both the PD-L1 expression and TIL infiltration is required for improving responses to the anti-PD-1/PD-L1 immunotherapy. Combination of anti-PD-1/PD-L1 with immune modulatory drugs, such as C-X-C chemokine receptor type 4 (CXCR4), poly (ADP-ribose) polymerase (PARP) or transforming growth factor (TGF)-β inhibitors has shown meaningful clinical benefits.

Keywords: Cytotoxic T lymphocyte associated antigen-4 (CTLA-4); Immune checkpoint inhibitor (ICI); Microsatellite instability (MSI); Mismatch repair; Programmed death ligand 1 (PD-L1); Programmed death-1 receptor (PD-1); Treatment-related adverse events (TRAEs); Tumor microenvironment (TME).