Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance

npj Precision Oncology, Год журнала: 2024, Номер 8(1)

Опубликована: Фев. 10, 2024

Abstract Tumor drug resistance emerges from the interaction of two critical factors: tumor cellular heterogeneity and immunosuppressive nature microenvironment (TME). Tumor-associated macrophages (TAMs) constitute essential components TME. M2-like TAMs are in facilitating metastasis as well augmenting tumors. This review encapsulates mechanisms that use to promote resistance. We also describe emerging therapeutic strategies currently targeting combination with other antitumor drugs, some still undergoing clinical trial evaluation. Furthermore, we summarize analyze various existing approaches for developing novel drugs target overcome resistance, highlighting how can effectively stop growth, metastasis,

Язык: Английский

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Tumor-associated macrophages: an effective player of the tumor microenvironment

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 16, 2023

Cancer progression is primarily caused by interactions between transformed cells and the components of tumor microenvironment (TME). TAMs (tumor-associated macrophages) make up majority invading immune components, which are further categorized as anti-tumor M1 pro-tumor M2 subtypes. While known to have anti-cancer properties, recognized extend a protective role tumor. As result, manipulates TME in such way that it induces macrophage infiltration switching bias secure its survival. This M2-TAM promotes cancer cell proliferation, neoangiogenesis, lymphangiogenesis, epithelial-to-mesenchymal transition, matrix remodeling for metastatic support, manipulation an immunosuppressive state. additionally promote emergence stem (CSCs), their ability originate, metastasize, relapse into tumors. CSCs also help revealing escape survival strategies during initiation phases. review describes reasons immunotherapy failure and, thereby, devises better impair tumor-TAM crosstalk. study will shed light on understudied TAM-mediated address much-needed holistic approach therapy, encompasses targeting cells, CSCs, all at same time.

Язык: Английский

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Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Июнь 11, 2024

Abstract Macrophages infiltrating tumour tissues or residing in the microenvironment of solid tumours are known as tumour-associated macrophages (TAMs). These specialized immune cells play crucial roles growth, angiogenesis, regulation, metastasis, and chemoresistance. TAMs encompass various subpopulations, primarily classified into M1 M2 subtypes based on their differentiation activities. macrophages, characterized by a pro-inflammatory phenotype, exert anti-tumoural effects, while with an anti-inflammatory function protumoural regulators. highly versatile respond to stimuli from other constituents within (TME), such growth factors, cytokines, chemokines, enzymes. induce polarization towards one phenotype another, leading complex interactions TME components influencing both pro-tumour anti-tumour processes. This review comprehensively deeply covers literature origin well intricate interplay between TME, dual nature promoting pro- Moreover, delves primary pathways implicated macrophage polarization, examining diverse that regulate this process. role shaping functions macrophages. In addition, advantages limitations current clinical interventions reviewed, including enhancing TAM phagocytosis, inducing exhaustion, inhibiting recruitment, polarizing M1-like phenotype. conclusion, treatment strategies targeting precision medicine show promise, overcoming several obstacles is still necessary achieve accessible efficient immunotherapy.

Язык: Английский

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Metabolic regulation of the immune system in health and diseases: mechanisms and interventions

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 9, 2024

Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes functions of immune cells. The regulation system is important in pathogenesis progression numerous diseases, such as cancers, autoimmune diseases diseases. concept immunometabolism was introduced over a decade ago to elucidate intricate interplay between metabolism immunity. definition has expanded from chronic low-grade inflammation reprogramming cells various With being proposed developed, can be gradually summarized becomes more clearer. In context many cancer, disease, occurs inducing proinflammatory or anti-inflammatory effects. phenotypic functional changes caused by further affect development Based on experimental results, targeting cellular promising therapy. this review, we focus introduce their pathways reprogramming, summarize how these effects We thoroughly explore targets treatments based existing studies. challenges translating results into clinical applications field are also summarized. believe that better understanding health will improve management most

Язык: Английский

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Macrophage plasticity: signaling pathways, tissue repair, and regeneration

MedComm, Год журнала: 2024, Номер 5(8)

Опубликована: Авг. 1, 2024

Abstract Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) alternatively (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay signaling pathways, transcriptional regulators, epigenetic modifications orchestrates polarization, allowing respond stimuli dynamically. Here, we provide comprehensive overview the cascades governing focusing on roles Toll‐like receptors, signal transducer activator transcription proteins, nuclear microRNAs. We also discuss emerging concepts metabolic reprogramming trained immunity, contributing their functional adaptability. Macrophage plasticity plays pivotal role in repair regeneration, macrophages coordinating inflammation, angiogenesis, matrix remodeling restore homeostasis. By harnessing potential novel therapeutic strategies targeting polarization could be developed for diseases, including chronic wounds, fibrotic disorders, inflammatory conditions. Ultimately, deeper understanding molecular mechanisms underpinning will pave way innovative regenerative medicine engineering approaches.

Язык: Английский

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Macrophage-mediated fracture healing: Unraveling molecular mechanisms and therapeutic implications using hydrogel-based interventions

Biomaterials, Год журнала: 2024, Номер 305, С. 122461 - 122461

Опубликована: Янв. 1, 2024

Язык: Английский

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

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 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.

Язык: Английский

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Noninvasive in vivo imaging of macrophages: understanding tumor microenvironments and delivery of therapeutics

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 26, 2025

Abstract Macrophages are pivotal in the body’s defense and response to inflammation. They present significant numbers widely implicated various diseases, including cancer. While molecular histological techniques have advanced our understanding of macrophage biology, their precise function within cancerous microenvironments remains underexplored. Enhancing knowledge macrophages dynamics extracellular vesicles (EVs) cancer development can potentially improve therapeutic management. Notably, also been harnessed deliver drugs. Noninvasive vivo imaging is crucial for investigating intricate cellular processes, comprehending underlying mechanisms tracking cells EVs’ migration, devising macrophage-dependent drug-delivery systems living organisms. Thus, has become an indispensable tool biomedical research. The integration multimodal approaches continued novel contrast agents hold promise overcoming current limitations expanding applications imaging. This study comprehensively reviews several methods labeling modalities, assessing merits drawbacks each approach. review concludes by offering insights into applicability real time monitoring preclinical clinical scenarios.

Язык: Английский

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Immunosuppression in Sepsis: Biomarkers and Specialized Pro-Resolving Mediators

Biomedicines, Год журнала: 2024, Номер 12(1), С. 175 - 175

Опубликована: Янв. 13, 2024

Severe infection can lead to sepsis. In sepsis, the host mounts an inappropriately large inflammatory response in attempt clear invading pathogen. This sustained high level of inflammation may cause tissue injury and organ failure. Later a paradoxical immunosuppression occurs, where is unable preexisting susceptible secondary infections. A major issue with sepsis treatment that it difficult for physicians ascertain which stage patient in. Sepsis will depend on patient’s immune status across spectrum disease, these statuses are nearly polar opposites early late stages Furthermore, there no approved resolve without contributing within host. Here, we review mechanisms sepsis-induced biomarkers immunosuppressive phase We focused reviewing three main These lymphocyte apoptosis, monocyte/macrophage exhaustion, increased migration myeloid-derived suppressor cells (MDSCs). The septic discuss include MDSC production/migration IL-10 levels, decreased counts HLA-DR expression, GPR18 expression. also literature use specialized pro-resolving mediators (SPMs) different models and/or as compounds have been reported being immunosuppressive. To obtain necessary information, searched PubMed database using keywords macrophage MDSCs, biomarkers, SPMs.

Язык: Английский

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Dissection of pro-tumoral macrophage subtypes and immunosuppressive cells participating in M2 polarization

Inflammation Research, Год журнала: 2024, Номер 73(9), С. 1411 - 1423

Опубликована: Июнь 27, 2024

Abstract Alternatively activated macrophage (M2) polarization can result in one of four subtypes based on cytokines and signaling pathways associated with activation: M2a, M2b, M2c, M2d macrophages. The majority M2 are anti-inflammatory pro-angiogenic, secreting growth factors (VEGF, PDGF) matrix metalloproteinases (MMP2, MMP9) which boost tumor growth, metastasis, invasion. M2-polarized macrophages immune suppressor cells harboring Myeloid derived cells, Regulatory T (Tregs), B as well alternatively (N2) neutrophils. Treg selectively support the metabolic stability, mitochondrial integrity, survival rate M2-like TAMs an indirect environment. Also, contribution Breg influences towards direction. TAM is when TAN levels microenvironment insufficient or vice versa, suggesting that its fine-tuned. Understanding functions suppressive mediators, involved will allow us to identify potential strategies for targeting repolarization phenotype innovative immunotherapy approaches. In this review, we have highlighted critical polarization, differential cytokine/chemokine profiles M1 subtypes, other cells’ impact within immunosuppressive niche.

Язык: Английский

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