- Academic Editor
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Objective: The use of immune
checkpoint inhibitors (ICIs) provides promising strategies for hepatocellular
carcinoma (HCC) treatment. This study aimed to explore impact and underlying
mechanism of the combination therapy of quercetin and anti-programmed cell death
1 (anti-PD-1) antibody on HCC. Methods: Orthotopically transplanted HCC
tumors in mice were treated with quercetin, anti-PD-1 antibody, or a combination
of both therapies. Histopathological changes and programmed cell death ligand 1
(PD-L1) expression were characterized by hematoxylin and eosin (H&E) and
immunohistochemistry (IHC) staining. The diversity and differences of gut
microbiota (GM) were evaluated through 16S rRNA sequencing. Levels of macrophage
immunity-related cytokines were quantified by enzyme-linked immunosorbent assay
(ELISA), quantitative real-time polymerase chain reaction (RT-qPCR), and Western
blot. Results: Combination therapy reduced necrosis,
fibrosis, and PD-L1 expression in liver tissues. Additionally, combination
therapy reduced GM imbalance and increased abundance of Firmicutes,
Actinobacteria, and Verrucomicrobiota at the phylum level as
well as Dubosiella and Akkermansia at the genus level.
Combination therapy improved macrophage immunity, raised the expressions of CD8a,
CD4, CD11b, interleukin (IL)-10, and interferon (IFN)-