Abstract
Background
This study performed a meta-analysis to evaluate the combined effects of polyphenols and anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors.
Methods
Relevant studies were collected from electronic databases. Standardized mean differences (SMDs) or hazard ratio (HR) was calculated by Stata 15.0 software.
Results
Sixteen preclinical studies were included. The overall meta-analysis showed that, compared to anti-PD-1/PD-L1 alone, polyphenol combined therapy significantly reduced the tumor volume (SMD = −3.28), weight (SMD = −2.18), number (SMD = −2.17), and prolonged the survival (HR = 0.45) of mice (all P < 0.001). Pooled analysis of mechanism studies indicated polyphenol combined therapy could increase the number of cytotoxic CD8+ T cells (SMD = 3.88; P < 0.001), IFN-γ+ CD8+ T cells (SMD = 2.38; P < 0.001), decrease the number of myeloid-derived suppressor cells (SMD = −2.52; P = 0.044) and Treg cells (SMD = −4.00; P = 0.004) and suppress PD-L1 expression in tumors (SMD = −13.41; P < 0.001). Subgroup analyses demonstrated curcuminoids, flavonoids, and stilbene changed the tumor volume, the percentage of CD8+ T cells, IFN-γ+CD8+ T cells, and PD-L1 expression.
Conclusion
Polyphenol supplementation may be a promising combined strategy for patients with poor response to anti-PD-1/PD-L1 monotherapy.
Author Contributions
YH and LZ conceived of the study idea. YH and ZY conducted the literature screening, data extraction, and statistical analysis. YH wrote the first draft of the manuscript. LZ revised the manuscript. All authors approved the final version to be published.
Disclosure Statement
All authors declare that they have no conflict of interest.
Data Availability Statement
The used data were included in the Supplementary Table S1.