Crosstalk between metabolism and epigenetics during macrophage polarization

Epigenetics & Chromatin, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 29, 2025

Macrophage polarization is a dynamic process driven by complex interplay of cytokine signaling, metabolism, and epigenetic modifications mediated pathogens. Upon encountering specific environmental cues, monocytes differentiate into macrophages, adopting either pro-inflammatory (M1) or anti-inflammatory (M2) phenotype, depending on the cytokines present. M1 macrophages are induced interferon-gamma (IFN-γ) characterized their reliance glycolysis role in host defense. In contrast, M2 stimulated interleukin-4 (IL-4) interleukin-13 (IL-13), favor oxidative phosphorylation participate tissue repair responses. Metabolism tightly linked to regulation, because key metabolic intermediates such as acetyl-coenzyme A (CoA), α-ketoglutarate (α-KG), S-adenosylmethionine (SAM), nicotinamide adenine dinucleotide (NAD+) serve cofactors for chromatin-modifying enzymes, which turn, directly influences histone acetylation, methylation, RNA/DNA protein arginine methylation. These control gene expression regulating chromatin accessibility, thereby modulating macrophage function polarization. Histone acetylation generally promotes more open structure conducive activation, while methylation can activate repress residue its state. Crosstalk between modifications, further fine-tunes phenotypes transcriptional networks response cues. While primarily functions epigenetics through degradation methylated proteins releases derivatives like asymmetric dimethylarginine (ADMA), contribute metabolism-a factor This review explores intricate relationships metabolism regulation during better understanding this crosstalk will likely generate novel therapeutic insights manipulating infections tuberculosis inflammatory diseases diabetes.

Language: Английский

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Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

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Mechanistic studies of tumor-associated macrophage immunotherapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 30, 2024

Tumor-associated macrophages (TAMs) are present in the tumor microenvironment and can polarize into subtypes with different functions characteristics response to stimuli, classifying them anti-tumorigenic M1-type pro-tumorigenic M2-type. The inhibit growth through release of pro-inflammatory cytokines, whereas M2-type contribute progression promotion proliferation, angiogenesis metastasis. Due duality macrophage effects on tumors, TAMs have been a hot topic research. In this paper, heterogeneity plasticity TAMs, interactions between other immune cells, tumors reviewed, therapeutic strategies for summarized discussed. These encompass methods approaches recruitment deplete modulate polarization TAMs. studies help deeply understand mechanism TAMs-tumor interaction provide reference combination therapy tumors.

Language: Английский

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Unraveling the Role of Fusobacterium nucleatum in Colorectal Cancer: Molecular Mechanisms and Pathogenic Insights

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 368 - 368

Published: Jan. 23, 2025

Fusobacterium nucleatum, a gram-negative anaerobic bacterium, has emerged as significant player in colorectal cancer (CRC) pathogenesis. The bacterium causes persistent inflammatory reaction the mucosa by stimulating release of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α, creating an environment conducive to progression. F. nucleatum binds penetrates epithelial cells through adhesins such FadA, impairing cell junctions encouraging epithelial-to-mesenchymal transition (EMT), which is associated with advancement. Additionally, modulates host immune system, suppressing activity conditions favorable for tumor growth. Its interactions gut microbiome contribute dysbiosis, further influencing carcinogenic pathways. Evidence indicates that can inflict DNA damage either directly via reactive oxygen species or indirectly environment. it triggers oncogenic pathways, especially Wnt/β-catenin signaling pathway, promotes growth longevity. Moreover, alters microenvironment, impacting behavior, metastasis, therapeutic responses. purpose this review elucidate molecular mechanisms contributes CRC. Understanding these crucial development targeted therapies diagnostic strategies CRC nucleatum.

Language: Английский

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Tumor Metastasis: Mechanistic Insights and Therapeutic Intervention

MedComm – Oncology, Journal Year: 2025, Volume and Issue: 4(1)

Published: Feb. 17, 2025

ABSTRACT Metastasis remains a leading cause of cancer‐related deaths, defined by complex, multi‐step process in which tumor cells spread and form secondary growths distant tissues. Despite substantial progress understanding metastasis, the molecular mechanisms driving this development effective therapies remain incompletely understood. Elucidating pathways governing metastasis is essential for discovery innovative therapeutic targets. The rapid advancements sequencing technologies expansion biological databases have significantly deepened our drivers associated drug resistance. This review focuses on particularly roles genetic mutations, epigenetic changes, post‐translational modifications progression. We also examine how microenvironment influences metastatic behavior explore emerging strategies, including targeted immunotherapies. Finally, we discuss future research directions, stressing importance novel treatment approaches personalized strategies to overcome improve patient outcomes. By integrating contemporary insights into basis innovation, provides comprehensive framework guide clinical cancer.

Language: Английский

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MMP28 recruits M2-type tumor-associated macrophages through MAPK/JNK signaling pathway-dependent cytokine secretion to promote the malignant progression of pancreatic cancer

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 19, 2025

Abstract Background Crosstalk between pancreatic cancer cells and tumor-associated macrophages (TAMs) is a critical driver of malignant progression, plays an important role in the low response rate to immunotherapy patients with for cancer. Although it known that induce TAM infiltration M2 polarization, underlying mechanisms remain elusive. Herein, we identified matrix metalloproteinase 28 (MMP28), highly expressed protein, as key regulator this process. Methods Immunohistochemical staining qRT-PCR were used validate MMP28 potential marker prognosis We evaluated tumor-promoting effect vitro CCK-8, Transwell, EdU assay Western blotting explored mechanism MMP28-induced polarization TAMs coculture system, immunofluorescence flow cytometry. A subcutaneous graft tumor model was constructed assess its ability infiltration. Results The relevant results study revealed strong correlation expression infiltration, predominance M2-polarized tissues. Mechanistic investigations demonstrated promotes secretion multiple cytokines, including IL-8 VEGFA through activation MAPK/JNK signaling pathway. These cytokines act potent chemoattractants polarizing factors TAMs. Additionally, discovered interaction ANXA2, which contributes regulation recruitment polarization. In vivo studies confirmed growth Depletion macrophages, inhibition JNK, or neutralization significantly suppressed progression. Transcriptomic analysis suggested by modulating amino acid metabolism. Conclusions Collectively, our findings elucidate novel manipulate microenvironment MMP28-dependent cytokine secretion, promoting highlight promising therapeutic target Graphical Schematic overview migration High levels promote mediating phosphorylation signalling pathway then recruiting subsequently metabolism alterations binding receptors on TAMs, ultimately phenotype. addition, ANXA2 increases MMP28-mediated interacting MMP28.

Language: Английский

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Reprogramming tumor-associated macrophages in gastric cancer: a pathway to enhanced immunotherapy

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

Gastric cancer (GC) remains a significant global health concern due to its poor prognosis and limited therapeutic options, particularly in advanced stages. Tumor microenvironment (TME), tumor-associated macrophages (TAMs), plays key role tumor progression, immune evasion, therapy resistance. TAMs exhibit plasticity, shifting between pro-inflammatory M1 immunosuppressive M2 phenotypes, with the latter predominating GC contributing outcomes. Recent advancements focus on targeting TAMs, including inhibiting polarization, reprogramming combining TAM-targeted approaches checkpoint inhibitors. Innovations nanotechnology, metabolic reprogramming, pathways such as interleukin-6 C-C motif ligand 2/C-C chemokine receptor 2 further enhance these strategies. However, challenges remain, spatial functional heterogeneity of within TME need for selective avoid disrupting homeostasis. Ongoing research TAM origins, functions, interactions is crucial developing precise effective therapies. These advances hold promise not only improving outcomes but also addressing other cancers similarly complex microenvironments.

Language: Английский

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Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Nov. 5, 2024

Chimeric antigen receptor (CAR)-T cell therapy demonstrates substantial efficacy in various hematological malignancies. However, its application solid tumors is still limited. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address challenges sliding cells. Despite improvements from fourth next-generation cells, new include systemic toxicity continuously secreted proteins, low productivity, elevated costs. Recent research targets genetic modifications boost killing potential, metabolic interventions hinder progression, diverse combination strategies enhance therapy. Efforts reduce duration cost developing allogenic in-vivo approaches, promising significant future advancements. Concurrently, innovative technologies platforms potential overcome limitations treating tumors. This review explores optimize therapies for tumors, focusing on enhancing overcoming restrictions. We summarize recent advances T subset selection, structural modifications, infiltration enhancement, interventions, production optimization, integration novel technologies, presenting therapeutic approaches that could improve therapy's applicability

Language: Английский

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Neutrophils’ dual role in cancer: from tumor progression to immunotherapeutic potential

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 140, P. 112788 - 112788

Published: July 30, 2024

Language: Английский

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Modulation of Tumor-Associated Macrophages to Overcome Immune Suppression in the Hepatocellular Carcinoma Microenvironment

Cancers, Journal Year: 2024, Volume and Issue: 17(1), P. 66 - 66

Published: Dec. 29, 2024

Hepatocellular carcinoma (HCC) is a major global health issue characterized by poor prognosis and complex tumor biology. One of the critical components HCC microenvironment (TME) tumor-associated macrophages (TAMs), which play pivotal role in modulating growth, immune evasion, metastasis. Macrophages are divided into two subtypes: pro-inflammatory M1 anti-inflammatory M2, both may exist TME with altered function proportion. The M2 further subdivided four distinct suppressive subsets. TAMs generally counted as M2-like functions that exert significant influence on cancer progression ability tumors to escape surveillance. Their involvement responses via different mechanisms at local systemic levels has made them key target for therapeutic interventions seeking enhance treatment outcomes. How TAMs’ depletion influences primary interest immunotherapies. purpose this review delve recent progress TAM-targeting therapies. We will explore current theories, benefits, challenges associated or inhibition. manuscript concludes future directions potential implications clinical practice.

Language: Английский

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