Development of natural products for anti-PD-1/PD-L1 immunotherapy against cancer

The programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint is one of the most promising therapeutic targets for cancer immunotherapy, but several challenges remain in current anti-PD-1/PD-L1 therapy. Natural products, mainly derived from traditional medicine, could improve and expand anti-PD-1/PD-L1 therapy because of their advantages such as large diversity and multi-target effects.This review summarize natural products, raw extracts, and traditional medicines with pharmacological effects associated with the PD-1/PD-L1 axis, particularly PD-L1.Electronic literature databases, including Web of Science, PubMed, and ScienceDirect, and online drugs and chemicals databases, including DrugBank, ZINC, PubChem, STITCH, and CTD, were searched without date limitation by February 2021. 'Natural product or herb or herbal plant or traditional medicine' and 'PD-L1' and 'Cancer immunotherapy' were used as the search keywords. Among 112 articles identified in database searching, 54 articles are full text articles, reporting in silico, in vitro, in vivo and clinical trials. 68 articles included are review articles and grey literature such as thesis and congress abstracts.Several natural products and traditional medicines have exhibited diverse and multi-functional effects including direct blockade of PD-1/PD-L1 interactions, modulation of PD-L1 expression, and cooperation with PD-1/PD-L1 inhibitors.Natural products and traditional medicines can facilitate the development of more effective and acceptable diverse strategies for anti-PD-1/PD-L1 therapy, but further exploration of natural products and pharmaceutical techniques is required.