Dihydroartemisinin increased the abundance of Akkermansia muciniphila by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD-1 immunotherapy

Zhang, Zhiqin; Shi, Xinli; Ji, Jingmin; Guo, Yinglin; Peng, Qing; Hao, Liyuan; Xue, Yu; Liu, Yiwei; Li, Caige; Lu, Junlan; Yu, Kun

doi:10.1007/s11684-022-0978-2

Cited by 5 publications

(10 citation statements)

References 52 publications

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“…Our recent research shows that dihydroartemisinin directly inhibits YAP1 in HCC, and YAP1 serves as a cellular target of dihydroartemisinin in HCC cells. Previous studies of our group have shown that dihydroartemisinin regulates lipid metabolism, TME, and intestinal microflora of the immune microenvironment through YAP1 in HCC, thus enhancing the effect of anti-PD-1 treatment ( 35 – 37 ). Firstly, anti-PD-1 therapy promotes lipid drop (LD) deposition in HCC, which may lead to ineffective anti-PD-1 treatment.…”

Section: Immunotherapy Strategy Of Targeting Yap1 For Liver Tumormentioning

confidence: 90%

“…Our previous research found that YAP1 suppression (knockdown or chemical inhibition) enhanced the effectiveness of anti-PD-1 immunotherapy in mice with liver tumors ( 34 ). This effect related to the suppression of immunosuppressive TME, the balance of intestinal microorganisms, and the homeostasis of lipid metabolism in HCC cells dependent on YAP1 ( 35 – 37 ).…”

Section: Introductionmentioning

confidence: 99%

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Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy

Gao,

Gong,

et al. 2024

Front. Immunol.

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Liver cancer is the third leading of tumor death, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Immune checkpoint inhibitors (ICIs) are yielding much for sufferers to hope for patients, but only some patients with advanced liver tumor respond. Recent research showed that tumor microenvironment (TME) is critical for the effectiveness of ICIs in advanced liver tumor. Meanwhile, metabolic reprogramming of liver tumor leads to immunosuppression in TME. These suggest that regulating the abnormal metabolism of liver tumor cells and firing up TME to turn “cold tumor” into “hot tumor” are potential strategies to improve the therapeutic effect of ICIs in liver tumor. Previous studies have found that YAP1 is a potential target to improve the efficacy of anti-PD-1 in HCC. Here, we review that YAP1 promotes immunosuppression of TME, mainly due to the overstimulation of cytokines in TME by YAP1. Subsequently, we studied the effects of YAP1 on metabolic reprogramming in liver tumor cells, including glycolysis, gluconeogenesis, lipid metabolism, arachidonic acid metabolism, and amino acid metabolism. Lastly, we summarized the existing drugs targeting YAP1 in the treatment of liver tumor, including some medicines from natural sources, which have the potential to improve the efficacy of ICIs in the treatment of liver tumor. This review contributed to the application of targeted YAP1 for combined therapy with ICIs in liver tumor patients.

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Section: Immunotherapy Strategy Of Targeting Yap1 For Liver Tumormentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy

Gao,

Gong,

et al. 2024

Front. Immunol.

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“…The strain of A. muciniphila was purchased from ATCC (BAA‐835). The culture methods were conducted according to our previous articles 17 . The concentration of suspended A. muciniphila was 1 × 10 8 CFU/mL after 48 h of anaerobic culture.…”

Section: Methodsmentioning

confidence: 99%

“…Then, the data were processed and analyzed according to CT value and by the 2 −ΔΔCT method. The primer sequences of total bacteria and A. muciniphila were used according to our previous articles 17 …”

Section: Methodsmentioning

confidence: 99%

“…10 Lycium barbarum polysaccharide (70% purity), yam polysaccharide (50% purity), and chrysanthemum polysaccharide (50% purity) were purchased from Shanxi Xintianyu Biotechnology. We divided the mice into seven groups at random, namely the ATB (0.1 mL normal saline), AKK (0.1 mL A. muciniphila, 1 × 10 8 CFU/mice), 17 WYC (0.467 g/mL wolfberry, 1.56 g/mL yam, and 0.389 g/mL chrysanthemum, 0.1 mL/mice), WYC+AKK (0.1 mL WYC solution and 0.1 mL A. muciniphila), LYC (0.026 g/mL 70% lycium barbarum polysaccharide, 0.036 g/mL 50% yam polysaccharide, and 50% chrysanthemum polysaccharide, 0.1 mL/mice), and LYC+AKK (0.1 mL LYC solution and 0.1 mL A. muciniphila) groups.…”

Section: Introductionmentioning

confidence: 99%

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Wolfberry, Yam, and Chrysanthemum polysaccharides increased intestinal Akkermansia muciniphila abundance and hepatic YAP1 expression to alleviate DILI

Lu,

Gong,

Gao

et al. 2023

The FASEB Journal

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Drug‐induced liver injury (DILI) is frequently induced by high dose of acetaminophen (APAP) and is concomitant with disturbances of gut flora. Akkermansia muciniphila is beneficial for the repair of liver injury. Lycium barbarum polysaccharide, yam polysaccharide, and chrysanthemum polysaccharide all have anti‐inflammatory and antioxidation effects. The objective of this study is to investigate the potential of lycium barbarum polysaccharide, yam polysaccharide, and chrysanthemum polysaccharide (LYC) in improving DILI by increasing the abundance of A. muciniphila. Initially, screening for the optimal concentrations of wolfberry, yam, and chrysanthemum (WYC) or LYC to promote A. muciniphila proliferation in vitro and validated in antibiotic (ATB)‐treated KM mice. Subsequently, APAP‐induced DILI model in BALB/c mice were constructed to examine the treatment effects of LYC. Our findings indicate that the optimal concentration ratio of WYC was 2:3:2, and LYC was 1:1:1. WYC increased A. muciniphila proliferation in vitro and in ATB‐treated mice under this ratio. Meanwhile, LYC increased A. muciniphila abundance in vitro and the combination LYC with A. muciniphila promoted the proliferation of A. muciniphila in ATB‐treated mice. The overdose of APAP resulted in the impairment of the intestinal barrier function and subsequent leakage of lipopolysaccharide (LPS). Moreover, LYC increased A. muciniphila abundance, reduced intestinal inflammation and permeability, and upregulated the expression of the tight junction protein zonula occludens protein 1 (ZO‐1) and occludin contents in the gut. Lastly, LYC inhibited LPS leakage and upregulated hepatic YAP1 expression, ultimately leading to the repair of DILI.

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The role of the gut microbiome in modulating immunotherapy efficacy in colorectal cancer

Zuo,

Huang,

Zou

2024

IUBMB Life

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This systematic literature review and meta‐analysis provide an overview of the critical role of gut microbiota in modulating the efficacy of immunotherapy for colorectal cancer. Gut microbes influence host immune responses through multiple mechanisms including modulation of immune cell activity, metabolite action, and immune tolerance. The ability of specific gut microbes to improve the efficacy of immune checkpoint inhibitors has been linked to their ability to improve gut barrier function, modulate immune cell activity, and produce key immunomodulatory metabolites such as short‐chain fatty acids. In addition, the composition and diversity of the gut microbiota are strongly associated with the efficacy of immunotherapies, demonstrating the potential to improve therapeutic response by modifying the gut microbiota. This paper also discusses the prospect of manipulating the gut microbiota through strategies such as fecal microbial transplantation, probiotic supplementation, and dietary modifications to optimize the efficacy of immunotherapy.

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Dihydroartemisinin increased the abundance of Akkermansia muciniphila by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD-1 immunotherapy

Cited by 5 publications

References 52 publications

Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy

Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy

Wolfberry, Yam, and Chrysanthemum polysaccharides increased intestinal Akkermansia muciniphila abundance and hepatic YAP1 expression to alleviate DILI

The role of the gut microbiome in modulating immunotherapy efficacy in colorectal cancer

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