Yupingfeng Granule Improves Th2‐Biased Immune State in Microenvironment of Hepatocellular Carcinoma through TSLP‐DC‐OX40L Pathway

Yao, Fei; Yuan, Qin; Song, Xiudao; Zhou, Liang; Liang, Guoqiang; Jiang, Guilin; Zhang, Lurong

doi:10.1155/2020/1263053

Cited by 14 publications

(13 citation statements)

References 34 publications

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“…This suggests the following corollary: MED8 may adjust Th2 cytokine levels, thereby promoting the metastasis and invasion of HCC. Other studies have shown that adjuvant T/Th2 cells, immature dendritic cells, and macrophages are negatively correlated with overall survival in patients with cancer [20], which may effectively explain the poorer prognosis in patients with highMED8 expression.…”

Section: Discussionmentioning

confidence: 97%

High Expression of Mediator Complex Subunit 8 Acts as a Prognostic Biomarker in Hepatocellular Carcinoma

Wu¹,

Cao

Luo

et al. 2021

Preprint

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Background : Mediator complex subunit 8 ( MED8 ) encodes a subunit of the mediator complex ( MED ), which is critical for transcription. MED8 is highly expressed in some tumours and is associated with a poor prognosis. However, correlations between MED8 and clinical features of hepatocellular carcinoma (HCC) have not been reported. Results: A univariate analysis showed that high MED8 expression predicts poor overall survival (HR: 2.495; 95% confidence interval (CI) 1.740, 3.578; P < 0.001). A multivariate regression analysis showed that high MED8 (HR: 3.032 (1.817, 5.060); P < 0.001) expression and M stage (HR=4.075 (1.179-14.091) for M1 vs. M0, P=0.026) are independent prognostic indicator of poor overall survival in patients with HCC. The areas under the curve (AUC) for receiver operating characteristic (ROC) curves were used to describe the prognostic value of MED8 (AUC: 0.905 (0.849, 0.941)). Gene Set Enrichment Analysis (GSEA) and Immune infiltration Analysis were applied to reveal significant enrichment differences among TCGA data. A functional analysis showed that the cell cycle checkpoints, mitotic G2-G2–M phases, transcriptional regulation by TP53, and regulation of TP53 activity were significantly enriched in DEGs associated with high MED8 expression. Th2 cells were positively correlated with MED8 expression. Conclusions: MED8 predicts poor prognosis in HCC, potentially via the regulation of the cell cycle regulation and Th2 cells. Key words: Mediator complex subunit 8, Mediator , hepatocellular carcinoma, prognosis, diagnostic biomarker

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Section: Discussionmentioning

confidence: 97%

High Expression of Mediator Complex Subunit 8 Acts as a Prognostic Biomarker in Hepatocellular Carcinoma

Wu¹,

Cao

Luo

et al. 2021

Preprint

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“…The result revealed that the high-risk group of both TCGA and ICGC datasets had higher contents of macrophages, Th2_cells, and Treg. It is widely accepted that macrophages [ 28 , 29 ], Th2_cells [ 30 ], and Treg [ 28 , 31 ] could promote tumor propagation and invasion and are associated with unfavorable prognosis. Especially, CD4+ CD25+ Foxp3+ regulatory T cells could secrete inhibitory cytokines (IL-10 and TGF- β ) to suppress NK cells and CD8+ T cells activity, resulting in T cell exhaustion and the defective antitumor effect [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Expression Signature from the Perspective of Mesenchymal-Epithelial Transition for Hepatocellular Carcinoma with Regard to Prognosis, Clinicopathological Features, Immune Cell Infiltration, Chemotherapeutic Efficacy, and Immunosuppressive Molecules

Zheng

2021

Journal of Oncology

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Purpose. Mesenchymal-epithelial transition (MET), a reverse biological process to epithelial-mesenchymal transition (EMT), is involved in tumor metastasis and invasion. However, the role of MET-related genes (MRGs) in hepatocellular carcinoma (HCC) prognosis remains unclear. Methods. In this research, we obtained MRGs data and clinical information from public databases. In the TCGA dataset, a prognostic signature for HCC was constructed by the least absolute shrinkage and selection operator (LASSO) method and externally verified using the ICGC dataset. Results. There were 148 differentially expressed MRGs (DEMRGs), out of which 37 MRGs were found associated with overall survival (OS) in the univariate Cox analysis. A novel signature integrating of 5 MRGs was constructed, which split patients into high- and low-risk groups. Kaplan–Meier analysis revealed that high-risk patients had unfavorable OS than those low-risk counterparts. Receiver operating characteristic curve (ROC) showed great performance of this signature in predictive ability. Multivariate Cox analysis confirmed that this signature could independently predict HCC prognosis. The analysis of immune cell infiltration demonstrated that immune status varied differently between high- and low-risk groups. The analysis of clinicopathological characteristics suggested that tumor grade, clinical stage, and T stage were different between risk groups. The analysis between this signature and chemotherapeutic efficacy and immunosuppressive molecules indicated that this signature could serve as a promising predictor. Conclusions. In conclusion, we constructed and verified a novel signature from the perspective of MET, which was significantly associated with HCC prognosis, clinicopathological features, immune status, chemotherapeutic efficacy, and immunosuppressive biomarkers.

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“…TSLP, an immunerelated factor, can activate DCs and involve in T cell differentiation, which raises the expression of Th2-polarizing molecule CD252 (OX40L), and induces Th2 response (42). Yao et al reported that YPF reduced the expression of TSLP and OX40L to induce the maturation of DCs and the expression of CD80, CD86, MHC-II as well as IL-12 (12). Furthermore, DCs combine with tumor cells to form fusion cells (FCs), which play an inhibitory role in tumor development.…”

Section: Dendritic Cells (Dcs)mentioning

confidence: 99%

“…The Th1 immune response can be usually inhibited in a variety of malignant tumors, which manifests as the down-regulation of TNF-α, IL-2, IFN-γ and IL-2, and defecting the proliferation of cytotoxic T cells, macrophages and NK cells. On the contrary, Th2-biased immune response is up-regulated in cancer progression ( 12 ). The cytokines IL-4, IL-5 and IL-13 secreted by Th2 cells have been found to facilitate tumor growth ( 13 ).…”

Section: Immune Cells In Tumor Microenvironmentmentioning

confidence: 99%

“…Yao et al. reported that YPF reduced the expression of TSLP and OX40L to induce the maturation of DCs and the expression of CD80, CD86, MHC-II as well as IL-12 ( 12 ). Furthermore, DCs combine with tumor cells to form fusion cells (FCs), which play an inhibitory role in tumor development.…”

Section: The Regulatory Effects Of Chinese Medicine Compounds On Innate Immune Cellsmentioning

confidence: 99%

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Anti-Tumor Effects of Chinese Medicine Compounds by Regulating Immune Cells in Microenvironment

Chen

Wang

et al. 2021

Front. Oncol.

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As the main cause of death in the world, cancer is one of the major health threats for humans. In recent years, traditional Chinese medicine has gained great attention in oncology due to the features of multi-targets, multi-pathways, and slight side effects. Moreover, lots of traditional Chinese medicine can exert immunomodulatory effects in vivo. In the tumor microenvironment, tumor cells, immune cells as well as other stromal cells often coexist. With the development of cancer, tumor cells proliferate uncontrollably, metastasize aggressively, and modulate the proportion and status of immune cells to debilitate the antitumor immunity. Reversal of immunosuppressive tumor microenvironment plays an essential role in cancer prevention and therapy. Immunotherapy has become the most promising strategy for cancer therapy. Chinese medicine compounds can stimulate the activation and function of immune cells, such as promoting the maturation of dendritic cells and inducing the differentiation of myeloid-derived suppressor cells to dendritic cells and macrophages. In the present review, we summarize and discuss the effects of Chinese medicine compounds on immune cells in the tumor microenvironment, including innate immune cells (dendritic cells, natural killer cells, macrophages, and myeloid-derived suppressor cells) and adaptive immune cells (CD4+/CD8+ T lymphocytes and regulatory T cells), and the various immunomodulatory roles of Chinese medicine compounds in cancer therapy such as improving tumor-derived inflammation, enhancing the immunity after surgery or chemotherapy, blocking the immune checkpoints, et al., aiming to provide more thoughts for the anti-tumor mechanisms and applications of Chinese medicine compounds in terms of tumor immunity.

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Yupingfeng Granule Improves Th2‐Biased Immune State in Microenvironment of Hepatocellular Carcinoma through TSLP‐DC‐OX40L Pathway

Cited by 14 publications

References 34 publications

High Expression of Mediator Complex Subunit 8 Acts as a Prognostic Biomarker in Hepatocellular Carcinoma

High Expression of Mediator Complex Subunit 8 Acts as a Prognostic Biomarker in Hepatocellular Carcinoma

A Novel Expression Signature from the Perspective of Mesenchymal-Epithelial Transition for Hepatocellular Carcinoma with Regard to Prognosis, Clinicopathological Features, Immune Cell Infiltration, Chemotherapeutic Efficacy, and Immunosuppressive Molecules

Anti-Tumor Effects of Chinese Medicine Compounds by Regulating Immune Cells in Microenvironment

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