Plasma Cell Polarization to the Immunoglobulin G Phenotype in Hepatocellular Carcinomas Involves Epigenetic Alterations and Promotes Hepatoma Progression in Mice

Yuan, Wei; Lao, Xiang-Ming; Xiao, Christos; Wang, Xuyan; Wu, Zong-Jian; Zeng, Qiu-Hui; Wu, Cai-Yuan; Wu, Ruiqi; Chen, Zhen-Xin; Zheng, Limin; Li, Bo; Kuang, Dong-Ming

doi:10.1053/j.gastro.2019.01.250

Cited by 89 publications

(76 citation statements)

References 38 publications

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“…It should be emphasized that depleting macrophages only abolishes their protumorigenic functions, but modulating the "context" of macrophages might restore their antitumorigenic properties. In support of this conclusion, we have recently observed that depleting B cells in hepatoma-bearing mice repurposed the macrophage polarization away from protumorigenic properties and toward antitumorigenic pathways and subsequently elicited antitumorigenic T cell responses (23,24,54). Analogously, NF-κB inhibitors in therapy may directly attenuate the growth of a tumor, but such a treatment also abrogates the activities of antitumorigenic effector T cells or APCs (55)(56)(57).…”

Section: Discussionmentioning

confidence: 81%

The local immune landscape determines tumor PD-L1 heterogeneity and sensitivity to therapy

Yuan¹,

Zhao²,

Gao³

et al. 2019

Journal of Clinical Investigation

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Section: Discussionmentioning

confidence: 81%

The local immune landscape determines tumor PD-L1 heterogeneity and sensitivity to therapy

Yuan¹,

Zhao²,

Gao³

et al. 2019

Journal of Clinical Investigation

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“… 169 The selection of adequate dosages and schedules may be particularly important in combinations between epidrugs and ICIs, as pro-tumorigenic effects have been recorded for both types of agents in experimental and clinical settings. 156 , 173 Therefore, administration strategies still need to be thoroughly addressed in carefully designed clinical studies. Another determinant for the optimal application of epigenetic therapies is the availability of epigenetic biomarkers.…”

Section: Discussionmentioning

confidence: 99%

“… 155 However, another recent report found that administration of decitabine and GSK126 resulted in an impaired antitumorigenic T cell response and increased growth of orthotopically implanted HCC cells. 156 Although, targeting G9a/KMT1C with different selective inhibitors reactivated TSG expression in HCC cells and demonstrated antitumoral effects in both in vitro and in vivo HCC xenograft models. 118 …”

Section: Targeting Epigenetic Mechanisms In Hccmentioning

confidence: 99%

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg

et al. 2020

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Summary Hepatocellular carcinoma (HCC) is a deadly tumour whose causative agents are generally well known, but whose pathogenesis remains poorly understood. Nevertheless, key genetic alterations are emerging from a heterogeneous molecular landscape, providing information on the tumorigenic process from initiation to progression. Among these molecular alterations, those that affect epigenetic processes are increasingly recognised as contributing to carcinogenesis from preneoplastic stages. The epigenetic machinery regulates gene expression through intertwined and partially characterised circuits involving chromatin remodelers, covalent DNA and histone modifications, and dedicated proteins reading these modifications. In this review, we summarise recent findings on HCC epigenetics, focusing mainly on changes in DNA and histone modifications and their carcinogenic implications. We also discuss the potential drugs that target epigenetic mechanisms for HCC treatment, either alone or in combination with current therapies, including immunotherapies.

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“…Many studies have discovered the prognostic role of B cells in CRC on malnutrition status, yet how the B cells regulated the malnutrition still remain unknown. We noticed both B cells and macrophages were regulated by these microbiota, and B cells, particularly plasma cells, could lead macrophages to polarization and differentiate into M1 like or M2 like macrophages, which present proin ammatory or pro-tumor effects via cytokine IL-17 or IL-10 secretion [6,26]. The in vivo results of C57BL/6J/6J model showed higher levels of M2b markers (IL-10 and CCL1) and M1 marker IL-12 in serum and intestinal tissue after FMT with malnutrition feces.…”

Section: Discussionmentioning

confidence: 99%

Malnutrition Accelerates Colorectal Cancer Progression through Macrophage Activated by B Cells Immune via Gut Microbiota

Xu¹,

Li²,

Wang³

et al. 2020

Preprint

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Background: Malnutrition threatened the clinical outcomes of colorectal cancer (CRC) by reducing patients’ responses to anti-cancer treatments and ultimately shortening thesurvival time. Recently malnutrition has been confirmed to play an important role in CRC progress via gut microbiota. However, roles of gut microbiota in the immunopathogenesis of malnutrition and its underlying mechanisms remain inconclusive. Methods: Patient-Generated Subjective Global Assessment (PG-SGA) was performed to determine the nutrition status in colon cancer patients. 16srRNA sequencing was prepared to explore the dramatic variation of the fecal microbiota among patients with different nutrition status. Fecal microbiota transplantation was used to transplant into C57BL/6J mice model and DSS/AOM mice model. Immunohistochemistry and immunofluorescence were applied to test the CD makers. Fluorescence-activated cell sorting was also prepared to explore the B cells and macrophage from serum and tissues. Enzyme-linked immunosorbent assay and qPCR were used to determine the expression level of cytokines.Results: In this work, we found the specific microbiota species including Atopobium.vaginae, Selenomonas.sputigena and Faecalibacterium.prausnitzii, which may be considered as the diagnostic biomarkers to help improve poor prognosis in CRC. These microbiota were found to be protumorigenic and adversely affect the nutritional status and overall survival of the animal models. More importantly, our evidence suggesting that these fecal microbiota recruited B cells and macrophage to activate the specific tumor immune in CRC. Depletion of B cells significantly suppressed fecal microbiota induced-M2b polarization, as well as the protumorigenic activity of tumor-associated macrophages in vivo.Conclusion: gut microbiome in CRC under malnutrition status could upregulate the activity of B cells and protumorigenic macrophage in CRC. Gut microbiome intervention could be a feasible approach to malnutrition-related CRC treatment.

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Plasma Cell Polarization to the Immunoglobulin G Phenotype in Hepatocellular Carcinomas Involves Epigenetic Alterations and Promotes Hepatoma Progression in Mice

Cited by 89 publications

References 38 publications

The local immune landscape determines tumor PD-L1 heterogeneity and sensitivity to therapy

The local immune landscape determines tumor PD-L1 heterogeneity and sensitivity to therapy

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg

Malnutrition Accelerates Colorectal Cancer Progression through Macrophage Activated by B Cells Immune via Gut Microbiota

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