Interactions between interleukin-6 and myeloid-derived suppressor cells drive the chemoresistant phenotype of hepatocellular cancer

Xu, Min; Zhao, Zhongwei; Song, Jingjing; Lan, Xilin; Lu, Shu‐Ling; Chen, Minjiang; Wang, Zufei; Chen, Weiqian; Fan, Xiaoxi; Wu, Fazong; Chen, Li; Tu, Jianfei; Ji, Jiansong

doi:10.1016/j.yexcr.2017.01.008

Cited by 64 publications

(43 citation statements)

References 24 publications

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“…Finally, we determined whether the miR-590-5p/YAP1 axis is correlated with chemotherapy response in HCC patients. For this experiment, needle tumor tissues obtained from 20 HCC patients with transarterial chemoembolization (TACE) were analyzed [ 28 ]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

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miR-590-5p suppresses hepatocellular carcinoma chemoresistance by targeting YAP1 expression

Chen

et al. 2018

EBioMedicine

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Background Resistance to chemotherapeutic treatment is a common phenomenon in cancers, especially in hepatocellular carcinoma (HCC). The Hippo signaling pathway has been demonstrated to play a role in tumor initiation, development, and progression. However, little is known about its roles in the HCC chemoresistance. Methods In this study, real-time PCR and western blotting were used to identify the expression profile of key components of Hippo signaling pathway between chemoresistant and chemosensitive HCC cell lines. In vitro and in vivo loss- and gain-of-function studies were performed to reveal the effects and related mechanism of microRNA-590-5p/YAP1 axis in the chemoresistant phenotype of HCC cells. Findings We identified yes-associated protein 1 (YAP1) as the major dysregulated molecules in adriamycin (ADR)-resistant HCC cells. YAP1 was profoundly implicated in the chemoresistant phenotype of HCC cells. Furthermore, microRNA-590-5p was revealed as a functional modulator of YAP1. Importantly, YAP1-mediated chemoresistant phenotype was closely related to increased expression of stemness markers and ATP-binding cassette transporters. HCC patients with poor response to transarterial chemoembolization (TACE) treatment had higher protein level of YAP1 than that in the responsive patients. Interpretation The microRNA-590-5p/YAP axis plays an important role in the chemotherapeutic resistance of HCC cells, suggesting new adjuvant chemotherapeutic directions in HCC. Fund National Natural Science Foundation of China, Zhejiang Province Medical and Health Care Key Project, Experimental Animal Science and Technology Projects of Zhejiang Province, Public Welfare Technology Application Research Project of Lishui, Chinese Medicine Science and Technology Projects of Zhejiang Province.

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Section: Resultsmentioning

confidence: 99%

“…The 20 patients received transarterial chemoembolization (TACE) in our hospital were enrolled and needle tissue samples were collected as reported previously [ 28 ]. All the process was performed in accordance with guidelines and regulations approved by the Fifth Affiliated Hospital of Wenzhou Medical University.…”

Section: Methodsmentioning

confidence: 99%

miR-590-5p suppresses hepatocellular carcinoma chemoresistance by targeting YAP1 expression

Chen

et al. 2018

EBioMedicine

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“…The high production of IL-6 and CCL5 in MAA-infected mice is most likely responsible for this accumulation. Both cytokines have been shown to induce proliferation of MDSC in tumors ( 48 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

Presence of Infected Gr-1intCD11bhiCD11cint Monocytic Myeloid Derived Suppressor Cells Subverts T Cell Response and Is Associated With Impaired Dendritic Cell Function in Mycobacterium avium-Infected Mice

Abdissa¹,

Nerlich²,

Beineke³

et al. 2018

Front. Immunol.

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Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with immunomodulatory function. To study the mechanism by which MDSC affect antimicrobial immunity, we infected mice with two M. avium strains of differential virulence, highly virulent Mycobacterium avium subsp. avium strain 25291 (MAA) and low virulent Mycobacterium avium subsp. hominissuis strain 104 (MAH). Intraperitoneal infection with MAA, but not MAH, caused severe disease and massive splenic infiltration of monocytic MDSC (M-MDSC; Gr-1intCD11bhiCD11cint) expressing inducible NO synthase (Nos2) and bearing high numbers of mycobacteria. Depletion experiments demonstrated that M-MDSC were essential for disease progression. NO production by M-MDSC influenced antigen-uptake and processing by dendritic cells and proliferation of CD4+ T cells. M-MDSC were also induced in MAA-infected mice lacking Nos2. In these mice CD4+ T cell expansion and control of infection were restored. However, T cell inhibition was only partially relieved and arginase (Arg) 1-expressing M-MDSC were accumulated. Likewise, inhibition of Arg1 also partially rescued T cell proliferation. Thus, mycobacterial virulence results in the induction of M-MDSC that block the T cell response in a Nos2- and Arg1-dependent manner.

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“…[44][45][46][47][48][49][50][51][52]. These evidence suggest that MDSCs contribute to the immunosuppressive network through multiple mechanisms and are potential immunotherapy targets for HCC.MDSCs from HCC patients are unable to stimulate an allogeneic T-cell response, suppress T-cell proliferation, and have high arginase activity.…”

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confidence: 98%

Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities

et al. 2019

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Incidence of hepatocellular carcinoma (HCC) is on the rise due to the prevalence of chronic hepatitis and cirrhosis. Although there are surgical and chemotherapy treatment avenues the mortality rate of HCC remains high. Immunotherapy is currently the new frontier of cancer treatment and the immunobiology of HCC is emerging as an area for further exploration. The tumor microenvironment coexists and interacts with various immune cells to sustain the growth of HCC. Thus, immunosuppressive cells play an important role in the anti-tumor immune response. This review will discuss the current concepts of immunosuppressive cells, including tumor-associated macrophages, marrow-derived suppressor cells, tumor-associated neutrophils, cancer-associated fibroblasts, and regulatory T cell interactions to actively promote tumorigenesis. It further elaborates on current treatment modalities and future areas of exploration.

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Interactions between interleukin-6 and myeloid-derived suppressor cells drive the chemoresistant phenotype of hepatocellular cancer

Cited by 64 publications

References 24 publications

miR-590-5p suppresses hepatocellular carcinoma chemoresistance by targeting YAP1 expression

miR-590-5p suppresses hepatocellular carcinoma chemoresistance by targeting YAP1 expression

Presence of Infected Gr-1intCD11bhiCD11cint Monocytic Myeloid Derived Suppressor Cells Subverts T Cell Response and Is Associated With Impaired Dendritic Cell Function in Mycobacterium avium-Infected Mice

Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities

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