Jianpi Huayu Decoction Attenuates the Immunosuppressive Status of H22 Hepatocellular Carcinoma-Bearing Mice: By Targeting Myeloid-Derived Suppressor Cells

Xie, Yingjie; Zhang, Yuan; Wei, Xiaohan; Zhou, Cheng; Huang, Yajing; Zhu, Xingwang; Chen, Yongxu; Wen, Huihong; Huang, Xuhui; Lin, Jingxia; Wang, Ziying; Ren, Yan; Fan, Baochao; Deng, Xian-Yu; Tan, Wei; Wang, Changjun

doi:10.3389/fphar.2020.00016

Cited by 20 publications

(17 citation statements)

References 38 publications

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“…The components of JHD were identi ed by HPLC-MS. Ten potential compounds, that is, Citropten 7, Formononetin, 1-Kestose, Biochanin A, Xanthohumol, Cytisine, Ferulic acid, Gallic acid Hesperetin, and Quercetin 3-O-glucoside were identi ed (Supplement 1A, Table 2), which were lined to what we identi ed before [7]. The characterizations and sources of these compounds are listed in Table 2.…”

Section: Identi Cation Of Components Of Jhdsupporting

confidence: 61%

“…JHD as a TCM formula, has been utilized in clinical for years. The application of JHD for the treatment of HCC has been studied in inducing apoptosis[6] and attenuates immunosuppressive status [21]. Sorafenib is still widely used for advanced HCC therapy.…”

Section: Discussionmentioning

confidence: 99%

“…It is used as an alternative and complementary therapy of liver-cancer. Previously, we showed that JHD inhibited the progression of HCC by inducing apoptosis [6] and immunomodulation [7]. Meanwhile, we noticed that the tumor-bearing mice treated with JHD were stronger than the mice with vehicle.…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Sorafenib with Jianpi Huayu Decoction Resulted in Tumor Regression and Prevented Adverse Events in Hepatocellular Carcinoma by Remodeling the Gut Microbiota

Deng¹,

Xie²,

Lu³

et al. 2021

Preprint

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Background: There is an urgent need for effective treatments for hepatocellular carcinoma (HCC). Sorafenib is first-line treatment for HCC, which has a modest efficacy due to severe adverse effects(AE), acquired resistance and others. Combination therapy may be able to overcome this limitation. Jianpi Huayu Decoction (JHD) is a traditional Chinese medicine formulation, which has been shown to be effective as an alternative and complementary therapy of HCC. We investigated the synergistic effect of JHD with sorafenib by a xenograft model.Methods: Growth of mouse-derived HCC cells and adverse events(AE) of treatment were evaluated in a subcutaneous model with JHD and clinical-dose sorafenib combination treatment. Diarrhea, the most frequently reported AE, was evaluated by diarrhea score. The gut microbiota(GM) composition of the mice was analyzed by Illumina NovaSeq. Results: JHD administration in mice synergistically enhanced the anti-tumor response, thereby suppressing HCC, and prevented occurrence of the most common AEs(diarrhea and body weight loss) of sorafenib. Sorafenib induced increased proinflammatory GM(Helicobacter) which promoted the progression of HCC and against anti-tumor treatment. JHD reduced the abundance of anti-inflammatory microbiota Muribaculum, Fusicatenibacter, and Dorea. Following the modulation of GM, the proinflammatory signaling interleukin 6/signal transducer and activator of transcription-3 pathway was downregulated by JHD.Conclusions: Our finding suggested that differences in the microbial gut flora may modulate resistance to sorafenib through IL-6/STAT3 signaling. JHD with microbiota modulation properties could potentiate sorafenib and provided a promising approach for HCC treatment.

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Section: Identi Cation Of Components Of Jhdsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

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Synergistic Sorafenib with Jianpi Huayu Decoction Resulted in Tumor Regression and Prevented Adverse Events in Hepatocellular Carcinoma by Remodeling the Gut Microbiota

Deng¹,

Xie²,

Lu³

et al. 2021

Preprint

Self Cite

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“…In fibrotic livers, hepatic stellate cell induced increasing of M-MDSCs was found to promote HCC growth in both patients and mice model via p38 MAPK signalling, while status can be rescued by molecular targeting blockage on this pathway [ 138 ]. A traditional chinese decoction therapy of jianpi huayu showed its regulatory potency on facilitating the differentiation of MDSCs into macrophages and DCs in HCC mice model, and alleviated the immunosuppression on CD4 + T cells, which unfolded new perspectives on DCs/MDSCs targeted treatment against PLC [ 139 ].…”

Section: Active Cellular Immunotherapy In Primary Liver Cancermentioning

confidence: 99%

Cellular based immunotherapy for primary liver cancer

Zheng

Jiao

et al. 2021

J Exp Clin Cancer Res

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Primary liver cancer (PLC) is a common malignancy with high morbidity and mortality. Poor prognosis and easy recurrence on PLC patients calls for optimizations of the current conventional treatments and the exploration of novel therapeutic strategies. For most malignancies, including PLC, immune cells play crucial roles in regulating tumor microenvironments and specifically recognizing tumor cells. Therefore, cellular based immunotherapy has its instinctive advantages in PLC therapy as a novel therapeutic strategy. From the active and passive immune perspectives, we introduced the cellular based immunotherapies for PLC in this review, covering both the lymphoid and myeloid cells. Then we briefly review the combined cellular immunotherapeutic approaches and the existing obstacles for PLC treatment.

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“…In H22 hepatocellular carcinoma-bearing mice, Jianpi Huayu decoction (JHD) significantly diminishes the destruction of spleen structure and the ratios of between Treg and Th17, and increases the ratios of CTL, DC, and MDSCs in the spleen. JHD also promotes the differentiation of IMCs into macrophages and mDCs, and weakens the expression of ROS in MDSCs to impair the inhibitory effect of those MDSCs on CD4+ T cell proliferation ( Xie et al, 2020 ) ( Figure 4 and Table 4 ). In 4T1 breast cancer mouse model, which is a suitable experimental animal model for human mammary cancer, artemisinin (ART) significantly promotes 4T1 tumor cell apoptosis and decreases TGF-β levels and the numbers of both MDSC and Treg to inhibit tumor growth in mice ( Cao Y. et al, 2019 ) ( Figure 4 and Table 4 ).…”

Section: The Impact Of Chm and Their Active Ingredients On Timps In Tmentioning

confidence: 99%

Impact of TCM on Tumor-Infiltrating Myeloid Precursors in the Tumor Microenvironment

Liu

Wang

Qiu

et al. 2021

Front. Cell Dev. Biol.

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The tumor microenvironment (TME) is composed of tumor cells, blood/lymphatic vessels, the tumor stroma, and tumor-infiltrating myeloid precursors (TIMPs) as a sophisticated pathological system to provide the survival environment for tumor cells and facilitate tumor metastasis. In TME, TIMPs, mainly including tumor-associated macrophage (TAM), tumor-associated dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs), play important roles in repressing the antitumor activity of T cell or other immune cells. Therefore, targeting those cells would be one novel efficient method to retard cancer progression. Numerous studies have shown that traditional Chinese medicine (TCM) has made extensive research in tumor immunotherapy. In the review, we demonstrate that Chinese herbal medicine (CHM) and its components induce tumor cell apoptosis, directly inhibiting tumor growth and invasion. Further, we discuss that TCM regulates TME to promote effective antitumor immune response, downregulates the numbers and function of TAMs/MDSCs, and enhances the antigen presentation ability of mature DCs. We also review the therapeutic effects of TCM herbs and their ingredients on TIMPs in TME and systemically analyze the regulatory mechanisms of TCM on those cells to have a deeper understanding of TCM in tumor immunotherapy. Those investigations on TCM may provide novel ideas for cancer treatment.

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Jianpi Huayu Decoction Attenuates the Immunosuppressive Status of H22 Hepatocellular Carcinoma-Bearing Mice: By Targeting Myeloid-Derived Suppressor Cells

Cited by 20 publications

References 38 publications

Synergistic Sorafenib with Jianpi Huayu Decoction Resulted in Tumor Regression and Prevented Adverse Events in Hepatocellular Carcinoma by Remodeling the Gut Microbiota

Synergistic Sorafenib with Jianpi Huayu Decoction Resulted in Tumor Regression and Prevented Adverse Events in Hepatocellular Carcinoma by Remodeling the Gut Microbiota

Cellular based immunotherapy for primary liver cancer

Impact of TCM on Tumor-Infiltrating Myeloid Precursors in the Tumor Microenvironment

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