3-Bromopyruvate inhibits the malignant phenotype of malignantly transformed macrophages and dendritic cells induced by glioma stem cells in the glioma microenvironment via miR-449a/MCT1

Sheng, Yujing; Jiang, Qianqian; Dong, Xuchen; Liu, Jiachi; Liu, Liang; Wang, Haiyang; Wang, Liping; Li, Haoran; Yang, Xuejun; Dong, Jun

doi:10.1016/j.biopha.2019.109610

Cited by 22 publications

(16 citation statements)

References 38 publications

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“…MCT1 is an important molecule that stimulates the IL-6/IL-6R/Stat3 axis and enhances M2 polarization in breast cancer ( 8 , 9 ). Additionally, utilizing 3-BrPA (a glycolysis inhibitor) to treat glioma suppressed the expression of MCT1 and regulated the progression of malignantly transformed macrophages ( 10 ). Type-I interferons (IFNs), such as IFN-α, IFN-β and others, are influenced by lactate and play an important role in elevating host immunity for cancer immune surveillance.…”

Section: Introductionmentioning

confidence: 99%

Prognostic implications of combined high expression of CD47 and MCT1 in breast cancer: a retrospective study during a 10-year period

Sun¹,

Liang²,

Li³

et al. 2022

Transl Cancer Res TCR

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Background: Clinical outcome after surgery of breast cancer needs more prognostic markers to predict currently. Cluster of differentiation 47 (CD47), due to its overexpression in various tumors and ability to inhibit phagocytosis, has been identified as a new immune checkpoint. Monocarboxylate transporter 1 (MCT1) is a protein involved in the immunomodulatory activities of the tumor microenvironment (TME) by maintaining the pH through aerobic glycolysis.Methods: We explored the expression of CD47 and MCT1 in breast invasive ductal carcinoma specimens to determine their association with prognosis. A total of 137 breast invasive ductal carcinoma tissues were collected for CD47 and MCT1 immunohistochemical staining.Results: Statistically analyzed, our study first indicated that in both univariate and multivariate analyses, the coexpression of CD47 and MCT1 was an independent prognostic factor for a poor 10-year overall survival rate (10-OS) and 10-year progression-free survival rate (10-DFS) (P<0.05). In addition, the combined high expression of these two markers also led to worse OS and PFS rates in the TNM (II + III), histologic grade (I + II), HER2 overexpression and basal-like subgroups. High expression of CD47 and MCT1 and combined high expression of CD47 and MCT1 were associated with clinicopathological parameters, such as histological grade, TNM stage, death status, and recurrence status in breast cancer patients. However, in the multivariate survival analysis, high expression of CD47 alone was not an independent prognostic factor for the 10-OS or the 10-DFS (P=0.104; P=0.153), and high expression of MCT1 alone was not an independent predictor for a poor 10-DFS (P=0.177) either. Conclusions:The coexpression of CD47 and MCT1 can serve as a prognostic biomarker leading to poor survival and an increased risk for recurrence, and this novel information could help guide the development of adjuvant therapy for breast cancer.

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Section: Introductionmentioning

confidence: 99%

Prognostic implications of combined high expression of CD47 and MCT1 in breast cancer: a retrospective study during a 10-year period

Sun¹,

Liang²,

Li³

et al. 2022

Transl Cancer Res TCR

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“…Promote immunosuppressive recruitment (Miska et al, 2019) Enhance lactate uptake of macrophages and DCs through MCT1 to induce the malignant transformation of macrophages and DCs Induce the tumorigenicity of immune cells (Sheng et al, 2020) IDH1/2 mutations Conversion of α-KG to 2-HG in TCA cycle…”

Section: Dendritic Cellsmentioning

confidence: 99%

“…Glioma cells recruited DCs through the CXC chemokine family ( Dastmalchi et al, 2019 ). Under the exposure to glioma cells expressing VEGF, the maturation of DCs were suppressed and antigen presentation and T-cell activation capabilities were diminished ( Sheng et al, 2020 ). What’s more, DCs in the glioma TME exhibited tumor tolerable properties, expressing more IDO to induce Tregs to infiltrate glioma tissues for immune escape ( Wainwright et al, 2014 ; He et al, 2015 ).…”

Section: Glioma Cell Metabolism Links To Immune Cells In Microenvironmentmentioning

confidence: 99%

“…The immune tolerance and malignant transformation of DCs were also related to glioma cell metabolism. By inhibiting glycolysis or LDHA, the proliferation, migration and infiltration into glioma tissues of malignantly transformed DCs were repressed ( Sheng et al, 2020 ), and these DCs secreted high levels of IL-12 to induce anti-tumor behavior of T cells ( Chirasani et al, 2013 ). In addition, DCs stayed in immature state and co-stimulatory molecules CD80 and CD86 were down-regulated owing to elevated secretion of VEGF from glioma cells ( Malo et al, 2018b ) expressing elevated metabolic enzymes ( He et al, 2015 ), involving HK2, PHGDH ( Wolf et al, 2011 ; Liu et al, 2013 ), HMGCR ( Slawinska-Brych et al, 2014 ), COX-2 ( Feng et al, 2017 ), nitric oxide (NO) metabolic regulation enzyme dimethylarginine dimethylaminohydrolase ( Boult et al, 2011 ) and mutated IDH1 ( Wang et al, 2014 ).…”

Section: Glioma Cell Metabolism Links To Immune Cells In Microenvironmentmentioning

confidence: 99%

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Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors

Qiu

Zhong

et al. 2021

Front. Cell Dev. Biol.

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During metabolic reprogramming, glioma cells and their initiating cells efficiently utilized carbohydrates, lipids and amino acids in the hypoxic lesions, which not only ensured sufficient energy for rapid growth and improved the migration to normal brain tissues, but also altered the role of immune cells in tumor microenvironment. Glioma cells secreted interferential metabolites or depriving nutrients to injure the tumor recognition, phagocytosis and lysis of glioma-associated microglia/macrophages (GAMs), cytotoxic T lymphocytes, natural killer cells and dendritic cells, promoted the expansion and infiltration of immunosuppressive regulatory T cells and myeloid-derived suppressor cells, and conferred immune silencing phenotypes on GAMs and dendritic cells. The overexpressed metabolic enzymes also increased the secretion of chemokines to attract neutrophils, regulatory T cells, GAMs, and dendritic cells, while weakening the recruitment of cytotoxic T lymphocytes and natural killer cells, which activated anti-inflammatory and tolerant mechanisms and hindered anti-tumor responses. Therefore, brain-targeted metabolic therapy may improve glioma immunity. This review will clarify the metabolic properties of glioma cells and their interactions with tumor microenvironment immunity, and discuss the application strategies of metabolic therapy in glioma immune silence and escape.

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“…They found that 3-BrPA significantly inhibited the proliferation of malignantly transformed macrophages and dendritic cells in a dose-dependent and time-dependent manner. Utilizing an online database and experimental data, they showed that 3-BrPA inhibits malignant progression via the miR-449a/MCT1 axis, which blocks lactate transport [ 255 ].…”

Section: Noncoding Rnas Regulate Both Tumor Metabolism and The Immune Microenvironmentmentioning

confidence: 99%

Noncoding RNAs link metabolic reprogramming to immune microenvironment in cancers

et al. 2021

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Altered metabolic patterns in tumor cells not only meet their own growth requirements but also shape an immunosuppressive microenvironment through multiple mechanisms. Noncoding RNAs constitute approximately 60% of the transcriptional output of human cells and have been shown to regulate numerous cellular processes under developmental and pathological conditions. Given their extensive action mechanisms based on motif recognition patterns, noncoding RNAs may serve as hinges bridging metabolic activity and immune responses. Indeed, recent studies have shown that microRNAs, long noncoding RNAs and circRNAs are widely involved in tumor metabolic rewiring, immune cell infiltration and function. Hence, we summarized existing knowledge of the role of noncoding RNAs in the remodeling of tumor metabolism and the immune microenvironment, and notably, we established the TIMELnc manual, which is a free and public manual for researchers to identify pivotal lncRNAs that are simultaneously correlated with tumor metabolism and immune cell infiltration based on a bioinformatic approach.

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3-Bromopyruvate inhibits the malignant phenotype of malignantly transformed macrophages and dendritic cells induced by glioma stem cells in the glioma microenvironment via miR-449a/MCT1

Cited by 22 publications

References 38 publications

Prognostic implications of combined high expression of CD47 and MCT1 in breast cancer: a retrospective study during a 10-year period

Prognostic implications of combined high expression of CD47 and MCT1 in breast cancer: a retrospective study during a 10-year period

Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors

Noncoding RNAs link metabolic reprogramming to immune microenvironment in cancers

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