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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Lung Tumor Cell-Derived Exosomes Promote M2 Macrophage Polarization

Cells, Год журнала: 2020, Номер 9(5), С. 1303 - 1303

Опубликована: Май 24, 2020

Cellular cross-talk within the tumor microenvironment (TME) by exosomes is known to promote progression. Tumor promoting macrophages with an M2 phenotype are suppressors of anti-tumor immunity. However, impact tumor-derived in modulating macrophage polarization lung TME largely unknown. Herein, we investigated if alter transcriptional and bioenergetic signatures M0 polarize them phenotype. The concentration produced p53 null H358 cells was significantly reduced compared A549 (p53 wild-type) cells, consistent p53-mediated regulation exosome production. In co-culture studies, internalized exosomes, differentiated into Importantly, demonstrate that enhance oxygen consumption rate macrophages, altering their state macrophages. vitro co-cultures demonstrated exosome-induced may be independent. Murine bone marrow marrow-derived myeloid-derived suppressor (MDSCs) co-cultured lewis carcinoma (LLC)-derived Collectively, these studies provide evidence for a novel role tumor-exosomes polarization, which then offers new therapeutic targets immunotherapy cancer.

Язык: Английский

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The Role of Exosomes and Their Applications in Cancer

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(22), С. 12204 - 12204

Опубликована: Ноя. 11, 2021

Exosomes are very small extracellular vesicles secreted by multiple cell types and extensively distributed in various biological fluids. Recent research indicated that exosomes can participate regulating the tumor microenvironment impacting proliferation progression. Due to extensive enrollment cancer development, have become a focus of search for new therapeutic method cancer. be utilized delivery molecules, proteins RNAs target cells with high efficiency. Exosome-carried proteins, lipids nucleic acids being tested as promising biomarkers diagnosis prognosis, even potential treatment targets Moreover, different sources exhibit performances applications. In this review, we elaborate on specific mechanism which affect communication between tumors state diagnostic applications cancers.

Язык: Английский

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The role of macrophage subtypes and exosomes in immunomodulation

Cellular & Molecular Biology Letters, Год журнала: 2022, Номер 27(1)

Опубликована: Окт. 3, 2022

Abstract Macrophages are influential members of the innate immune system that can be reversibly polarized by different microenvironment signals. Cell polarization leads to a wide range features, involving migration, development, and organization cells. There is mounting evidence macrophage plays key role in initiation development diseases. This study aims give an overview polarization, their subtypes, importance alternatively activated M2 classically M1 responses pathological conditions. review provides insight on exosomes M1/M2-like potential as promising therapeutic candidate.

Язык: Английский

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Exosome-Mediated Immunosuppression in Tumor Microenvironments

Cells, Год журнала: 2022, Номер 11(12), С. 1946 - 1946

Опубликована: Июнь 16, 2022

Exosomes are membranous structures secreted by nearly all cell types. As critical messengers for intercellular communication, exosomes deliver bioactive cargoes to recipient cells and involved in multiple physiopathological processes, including immunoregulation. Our pioneering study revealed that cancer release programmed death-ligand 1-positive into the circulation counter antitumor immunity systemically via T cells. Tumor cell-derived (TDEs) also play an immunosuppressive role other immunocytes, dendritic (DCs), macrophages, natural killer (NK) cells, myeloid-derived suppressor (MDSCs). Moreover, nontumor tumor microenvironments (TMEs) exert effects. This review systematically provides a summary of immunosuppression induced microenvironments, which modulates growth, invasion, metastasis, immunotherapeutic resistance. Additionally, therapeutic strategies targeting molecular mechanism exosome-mediated development, may help overcome several obstacles, such as immune tolerance oncotherapy, discussed. Detailed knowledge specific functions contribute development innovative treatments.

Язык: Английский

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Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway

International Journal of Biological Sciences, Год журнала: 2022, Номер 18(8), С. 3209 - 3222

Опубликована: Янв. 1, 2022

Tumor-derived exosomes play a pivotal role in regulating tumor progression by mediating crosstalk between cells and immune such as macrophages within the microenvironment. Macrophages can adopt two distinct polarization statuses switch M1 or M2 activation phenotypes response to different external stimuli. However, of derived macrophage phenotypic development have not been elucidated renal cell carcinoma (RCC). Here we found that high infiltration was associated with worse prognosis RCC patients, therefore propose our hypothesis might directly influence thus promote progression. Both cell-based vitro models orthotopic transplantation vivo were constructed ELISA, flow cytometry, functional studies performed investigate whether how RCC-derived regulate growth. The results these polarization, cytokine release, phagocytosis, angiogenesis, development. Further study revealed amount recently discovered lncRNA called lncARSR exosomes. Overexpression induced changes promoted growth vivo, while knockdown siRNA disrupted exosomes-mediated polarization. LncARSR interacts miR-34/miR- 449 increase STAT3 expression mediate cells. Together, facilitate through inducing via transferring lncARSR, suggesting exosomes, are potential therapeutic targets for treatment RCC.

Язык: Английский

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Exosome-mediated tumor metastasis: Biology, molecular targets and immuno-therapeutic options

Pathology - Research and Practice, Год журнала: 2024, Номер 254, С. 155083 - 155083

Опубликована: Янв. 3, 2024

Язык: Английский

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Role of exosomal miRNAs and macrophage polarization in gastric cancer: a novel therapeutic strategy

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177268 - 177268

Опубликована: Янв. 1, 2025

Язык: Английский

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Macrophages in pancreatitis: Mechanisms and therapeutic potential

Biomedicine & Pharmacotherapy, Год журнала: 2020, Номер 131, С. 110693 - 110693

Опубликована: Сен. 1, 2020

Macrophages play a crucial role in the pathogenesis of pancreatitis that is common gastrointestinal disease. Particularly, macrophages differentiate into different phenotypes and exert diverse functions acute (AP) chronic (CP), respectively. In AP, pancreas other related organs are mainly activated differentiated pro-inflammatory M1 phenotype, furthermore secrete inflammatory cytokines mediators, causing local inflammation pancreas, even intractable systemic response or multiple organ failure. CP, often exhibit M2 polarisation interact with pancreatic stellate cells (PSCs) an autocrine paracrine cytokine-dependent manner to promote progression fibrosis. As severity fibrosis aggravates, proportion M2/M1 macrophage increases. The discovery has promoted research targeted drugs, which provides great potential for effective treatment pancreatitis. This paper overview roles various current status immunotherapy targeting macrophages. findings addressed this review considerable significance understanding pivotal

Язык: Английский

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The roles of tumor-derived exosomes in altered differentiation, maturation and function of dendritic cells

Molecular Cancer, Год журнала: 2021, Номер 20(1)

Опубликована: Июнь 2, 2021

Abstract Tumor-derived exosomes (TDEs) have been shown to impede anti-tumor immune responses via their immunosuppressive cargo. Since dendritic cells (DCs) are the key mediators of priming and maintenance T cell-mediated responses; thus it is logical that released by tumor can exert a dominant influence on DCs biology. This paper intends provide mechanistic insight into TDEs-mediated abnormalities in context. More importantly, we discuss extensively how induce subversion differentiation, maturation function separate sections. We also briefly describe importance TDEs at therapeutic level help guide future treatment options, particular DC-based vaccination strategy, review advances design discovery exosome inhibitors. Understanding exosomal content pathways which responsible for evasion may revise rationales devise novel approaches overcome hurdles cancer treatment.

Язык: Английский

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