Research Progress on Combination Therapies Based on PD-1/PD-L1 Blockade Against Malignancies and the Adjuvant Effects of Traditional Chinese Medicine

Programmed death (PD-1) is an important immune checkpoint receptor expressed on the surface of T cells, B cells and natural killer (NK) cells. PD-L1 (B7-H1) is a critical ligand for PD-1, and is widely expressed in a variety of cancer cells, immune cells, and normal histocytes. It has been established that the PD-1/PD-L1 interaction can produce an immunosuppressive effect by suppressing T cell proliferation, cytokine secretion, and cytotoxicity. Currently, PD-1 and PD-L1 inhibitors are known to be promising anticancer agents that reverse the antitumor immune function of T cells by inhibiting the PD-1/PD-L1 axis. The monotherapy of PD-1/PD-L1 blockade, while effective in treating cancers, is limited by a low response rate, immune-related adverse events (irAEs), and drug resistance. Their combinations with surgery, chemotherapy, radiotherapy, immunotherapy, hormone therapy, and traditional Chinese medicine (TCM), due to a synergistic effect, have broadened the frontier of cancer research. Following a holistic principle, TCM serves as an adjuvant therapy with PD-1/PD-L1 blockade, and provides benefits through complicated mechanisms. We specifically focused on the profound significance of TCM's assistance of PD-1/PD-L1 blockade, and the opportunities and challenges of treating cancers with both TCM and PD-1/PD-L1 blockade.