Phosphatidylserine released from apoptotic cells in tumor induces M2‐like macrophage polarization through the PSR‐STAT3‐JMJD3 axis

Liang, Xiao; Luo, Min; Shao, Bin; Yang, Jingyun; An, Tong; Wang, Ruibo; Liu, Yantong; Ren, Jun; Liu, Ting; Yi, Tao; Zhao, Xia; Wei, Yuquan; Wei, Xiawei

doi:10.1002/cac2.12272

Cited by 27 publications

(13 citation statements)

References 50 publications

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“…In addition, it has been reported that Jumonji domain containing 3 (Jmjd3) is essential for M2 macrophage polarization, and IRF4 is a Jmjd3 target gene ( 110 , 114 ). Phosphatidylserine released by apoptotic tumor cells could induce the polarization and accumulation of M2 macrophages via a STAT3-Jmjd3-IRF4 signaling axis ( 115 ); therefore, down-regulation of Jmjd3 by targeting the STAT3-Jmjd3-IRF4 axis may be a candidate approach for inhibiting the accumulation of M2 macrophages in tumor sites and remodeling the TME. Moreover, some miRNAs have been found to promote the transformation of macrophages from M2 to M1 by targeting IRF4 to activate IRF5 ( 116 , 117 ).…”

Section: Regulation Of Irf4 In Immunosuppressive Cells In the Tmementioning

confidence: 99%

Regulatory effects of IRF4 on immune cells in the tumor microenvironment

Liang²,

Li³

et al. 2023

Front. Immunol.

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The tumor microenvironment (TME) is implicated in tumorigenesis, chemoresistance, immunotherapy failure and tumor recurrence. Multiple immunosuppressive cells and soluble secreted cytokines together drive and accelerate TME disorders, T cell immunodeficiency and tumor growth. Thus, it is essential to comprehensively understand the TME status, immune cells involved and key transcriptional factors, and extend this knowledge to therapies that target dysfunctional T cells in the TME. Interferon regulatory factor 4 (IRF4) is a unique IRF family member that is not regulated by interferons, instead, is mainly induced upon T-cell receptor signaling, Toll-like receptors and tumor necrosis factor receptors. IRF4 is largely restricted to immune cells and plays critical roles in the differentiation and function of effector cells and immunosuppressive cells, particularly during clonal expansion and the effector function of T cells. However, in a specific biological context, it is also involved in the transcriptional process of T cell exhaustion with its binding partners. Given the multiple effects of IRF4 on immune cells, especially T cells, manipulating IRF4 may be an important therapeutic target for reversing T cell exhaustion and TME disorders, thus promoting anti-tumor immunity. This study reviews the regulatory effects of IRF4 on various immune cells in the TME, and reveals its potential mechanisms, providing a novel direction for clinical immune intervention.

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Section: Regulation Of Irf4 In Immunosuppressive Cells In the Tmementioning

confidence: 99%

Regulatory effects of IRF4 on immune cells in the tumor microenvironment

Liang²,

Li³

et al. 2023

Front. Immunol.

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“…Higher expression of phosphatidylserine synthases results in a greater amount of PS in cancer cells, which exposes macrophages to a higher amount of PS during apoptosis [ 163 ]. This leads to the polarization of macrophages into M2 macrophages [ 164 ], which participate in tumorigenesis. Thus, higher expression of phosphatidylserine synthases increases the amount of PS in cancer cells, which upon apoptosis, more strongly polarizes macrophages into M2 macrophages, leading to intensified tumorigenesis and a worse prognosis for cancer patients.…”

Section: Synthesis Of Glycerophospholipids and Glioblastoma Tumorigen...mentioning

confidence: 99%

Biosynthesis and Significance of Fatty Acids, Glycerophospholipids, and Triacylglycerol in the Processes of Glioblastoma Tumorigenesis

Korbecki

Bosiacki

Gutowska

et al. 2023

Cancers

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One area of glioblastoma research is the metabolism of tumor cells and detecting differences between tumor and healthy brain tissue metabolism. Here, we review differences in fatty acid metabolism, with a particular focus on the biosynthesis of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) by fatty acid synthase (FASN), elongases, and desaturases. We also describe the significance of individual fatty acids in glioblastoma tumorigenesis, as well as the importance of glycerophospholipid and triacylglycerol synthesis in this process. Specifically, we show the significance and function of various isoforms of glycerol-3-phosphate acyltransferases (GPAT), 1-acylglycerol-3-phosphate O-acyltransferases (AGPAT), lipins, as well as enzymes involved in the synthesis of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and cardiolipin (CL). This review also highlights the involvement of diacylglycerol O-acyltransferase (DGAT) in triacylglycerol biosynthesis. Due to significant gaps in knowledge, the GEPIA database was utilized to demonstrate the significance of individual enzymes in glioblastoma tumorigenesis. Finally, we also describe the significance of lipid droplets in glioblastoma and the impact of fatty acid synthesis, particularly docosahexaenoic acid (DHA), on cell membrane fluidity and signal transduction from the epidermal growth factor receptor (EGFR).

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“…For example, it has been well-known that functional loss of Ink4B/p15-ARF/p14-INK4A/p16 is an important inducing factor for tumorigenesis in multiple cancer types, and JMJD3 has been reported to promote the expression of tumor suppressors p16 and P14 ( 167 ). Studies have shown that JMJD3 is involved in inducing polarization of M2-like macrophages and thus participates in tumor progression ( 168 ). Taken together, considering the promoting roles of inflammatory factors in cancer ( 169 ), it might be reasonable to speculate that blocking JMJD3 may serve as an entry point for targeted therapy of chronic inflammation or even as a novel antitumor target for inflammation-related cancers.…”

Section: Functional Mechanisms Of Jmjd Histone Demethylases In Cancer...mentioning

confidence: 99%

The JMJD Family Histone Demethylases in Crosstalk Between Inflammation and Cancer

Jia

Zhang

et al. 2022

Front. Immunol.

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Inflammation has emerged as a key player in regulating cancer initiation, progression, and therapeutics, acting as a double edged sword either facilitating cancer progression and therapeutic resistance or inducing anti-tumor immune responses. Accumulating evidence has linked the epigenetic modifications of histones to inflammation and cancer, and histone modifications-based strategies have shown promising therapeutic potentials against cancer. The jumonji C domain-containing (JMJD) family histone demethylases have exhibited multiple regulator functions in inflammatory processes and cancer development, and a number of therapeutic strategies targeting JMJD histone demethylases to modulate inflammatory cells and their products have been successfully evaluated in clinical or preclinical tumor models. This review summarizes current understanding of the functional roles and mechanisms of JMJD histone demethylases in crosstalk between inflammation and cancer, and highlights recent clinical and preclinical progress on harnessing the JMJD histone demethylases to regulate cancer-related inflammation for future cancer therapeutics.

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Phosphatidylserine released from apoptotic cells in tumor induces M2‐like macrophage polarization through the PSR‐STAT3‐JMJD3 axis

Cited by 27 publications

References 50 publications

Regulatory effects of IRF4 on immune cells in the tumor microenvironment

Regulatory effects of IRF4 on immune cells in the tumor microenvironment

Biosynthesis and Significance of Fatty Acids, Glycerophospholipids, and Triacylglycerol in the Processes of Glioblastoma Tumorigenesis

The JMJD Family Histone Demethylases in Crosstalk Between Inflammation and Cancer

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