Macrophage Polarization and Its Role in Liver Disease

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 14, 2021

Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity polarization. Under pathological conditions, addition to the resident macrophages, other macrophages also recruited diseased tissues, polarize various phenotypes (mainly M1 M2) under stimulation of factors microenvironment, thus playing different roles functions. Liver diseases hepatic changes caused by a variety pathogenic (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic disease, metabolic-associated fatty fibrosis, hepatocellular carcinoma. Recent studies shown that macrophage polarization plays an role initiation development diseases. However, because both pathogenesis complex, mechanism need be further clarified. Therefore, origin mechanisms reviewed first this paper. It is found involves several molecular mechanisms, mainly TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, miRNA signaling pathways. In addition, paper expounds diseases, which aims provide references for research contributing therapeutic strategy ameliorating modulating

Language: Английский

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Stromal cells in the tumor microenvironment: accomplices of tumor progression?

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(9)

Published: Sept. 4, 2023

Abstract The tumor microenvironment (TME) is made up of cells and extracellular matrix (non-cellular component), cellular components include cancer non-malignant such as immune stromal cells. These three types establish complex signals in the body further influence genesis, development, metastasis participate resistance to anti-tumor therapy. It has attracted scholars study TME due significant efficacy checkpoint inhibitors (ICI) chimeric antigen receptor T (CAR-T) solid tumors hematologic tumors. After more than 10 years efforts, role strategy treating based on have developed rapidly. Moreover, ICI been recommended by guidelines first- or second-line treatment strategies a variety At same time, another major class TME, which also play very important metabolism, growth, metastasis, evasion resistance. Stromal can be recruited from neighboring non-cancerous host formed transdifferentiation they development drug secreting various factors exosomes, participating angiogenesis regulating response matrix. However, with deepening understanding cells, people found that not only effect promoting but inhibit some cases. In this review, we will introduce origin well specific mechanism tumorigenesis for We focus tumor-associated fibroblasts (CAFs), mesenchymal stem (MSCs), adipocytes (CAAs), endothelial (TECs) pericytes (PCs)

Language: Английский

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CAFs orchestrates tumor immune microenvironment—A new target in cancer therapy?

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 14, 2023

Cancer immunotherapy has opened a new landscape in cancer treatment, however, the poor specificity and resistance of most targeted therapeutics have limited their therapeutic efficacy. In recent years, role CAFs immune regulation been increasingly noted as more evidence uncovered regarding link between cancer-associated fibroblasts (CAFs) evolutionary process tumor progression. interact with cells to shape microenvironment (TIME) that favors malignant progression, crosstalk leads failure immunotherapies. this review, we outline advances immunosuppressive function CAFs, highlight mechanisms CAFs-immune cell interactions, discuss current CAF-targeted strategies for future study.

Language: Английский

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From gatekeepers to providers: regulation of immune functions by cancer-associated fibroblasts

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(5), P. 421 - 443

Published: March 2, 2023

Language: Английский

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Tumor-derived Cav-1 promotes pre-metastatic niche formation and lung metastasis in breast cancer

Theranostics, Journal Year: 2023, Volume and Issue: 13(5), P. 1684 - 1697

Published: Jan. 1, 2023

Rationale: Breast cancer (BC), as one of the most frequently diagnosed cancer, has a poor prognosis due to development distant metastasis. Among BC metastatic sites, lung is common sites. Caveolin-1 (Cav-1) functional membrane protein that plays vital role in tumor Although studies have revealed Cav-1 levels were elevated patients with advanced whether affects metastasis by influencing formation pre-metastatic niche (PMN) through exosomes not been explored. Methods: Differential ultracentrifugation, transmission electron microscopy and nanoparticle tracking analysis used verify presence exosomes. Transwell assays examine biological effects containing Cav-1. Both vitro cell cultures mammary cell-induced mouse models assess The regulatory mechanisms PMN using western blot, flow cytometry, RT-qPCR, immunofluorescence assays, gene overexpression RNA interference assays. Results: Exosomes critical functions transporting between primary organ microenvironments. BC-derived can act signaling molecule mediate intercellular communication regulate before regulating expression marker genes inflammatory chemokines epithelial cells, promoting secretion tenascin-C (TnC) fibroblasts cause extracellular matrix (ECM) deposition, inhibiting PTEN/CCL2/VEGF-A pathway macrophages facilitate their M2-type polarization angiogenesis. Conclusion: Our study investigated induced data may provide new directions for exploring developing treatment strategies

Language: Английский

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Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment advanced HCC, but problems such as drug resistance immune-related adverse events still exist in clinical practice. immunosuppressive tumor microenvironment (TME) HCC restricts efficacy essential for progression metastasis. Therefore, it necessary to elucidate mechanisms behind TME develop apply immunotherapy. This review systematically summarizes pathogenesis formation TME, by which accelerates We also status further discuss existing challenges potential therapeutic strategies targeting TME. hope inspire optimizing innovating immunotherapeutic comprehensively understanding structure function HCC.

Language: Английский

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Dynamic interactions in the tumor niche: how the cross-talk between CAFs and the tumor microenvironment impacts resistance to therapy

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 22, 2024

The tumor microenvironment (TME) is a complex ecosystem of cells, signaling molecules, and extracellular matrix components that profoundly influence cancer progression. Among the key players in TME, cancer-associated fibroblasts (CAFs) have gained increasing attention for their diverse influential roles. CAFs are activated found abundantly within TME various types. contribute significantly to progression by promoting angiogenesis, remodeling matrix, modulating immune cell infiltration. In order microenvironment, engage cross-talk with other stromal through paracrine direct cell-cell interactions. This can result immunosuppression, proliferation, epithelial-mesenchymal transition, contributing disease Emerging evidence suggests play crucial role therapy resistance, including resistance chemotherapy radiotherapy. modulate response treatment secreting factors promote drug efflux, enhance DNA repair mechanisms, suppress apoptosis pathways. paper aims understand multifaceted functions discusses between sheds light on contibution resistance. Targeting or disrupting cells holds promise overcoming improving efficacy

Language: Английский

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Signaling pathways in the regulation of cancer stem cells and associated targeted therapy

MedComm, Journal Year: 2022, Volume and Issue: 3(4)

Published: Oct. 5, 2022

Cancer stem cells (CSCs) are defined as a subpopulation of malignant tumor with selective capacities for initiation, self-renewal, metastasis, and unlimited growth into bulks, which believed major cause progressive phenotypes, including recurrence, treatment failure. A number signaling pathways involved in the maintenance cell properties survival CSCs, well-established intrinsic pathways, such Notch, Wnt, Hedgehog signaling, extrinsic vascular microenvironment tumor-associated immune cells. There is also intricate crosstalk between these signal cascades other oncogenic pathways. Thus, targeting pathway molecules that regulate CSCs provides new option therapy-resistant or -refractory tumors. These treatments include small molecule inhibitors, monoclonal antibodies target key well CSC-directed immunotherapies harness systems to CSCs. This review aims provide an overview regulating networks their interactions CSC development. We address update on development therapeutics, special focus those application approval under clinical evaluation.

Language: Английский

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Advances of cancer-associated fibroblasts in liver cancer

Biomarker Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: Aug. 16, 2022

Abstract Liver cancer is one of the most common malignant tumors worldwide, it ranked sixth in incidence and fourth mortality. According to distinct origin tumor cells, liver mainly divided into hepatocellular carcinoma (HCC) cholangiocarcinoma (CCA). Since cases are diagnosed at an advanced stage, prognosis poor. Tumor growth depends on dynamic interaction various cellular components microenvironment (TME). As abundant stroma, cancer-associated fibroblasts (CAFs) have been involved progression cancer. The interplay between CAFs immune or vascular endothelial cells TME through direct cell-to-cell contact indirect paracrine interaction, affects initiation development tumors. Additionally, not a homogeneous cell population Recently, single-cell sequencing technology has used help better understand diversity In this review, we update knowledge both HCC CCA, including their origins, chemoresistance, stemness induction, formation, role CAFs. Understanding context-dependent different subsets provides new strategies for precise treatment.

Language: Английский

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Emerging Role of Cancer-Associated Fibroblasts in Progression and Treatment of Hepatocellular Carcinoma

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3941 - 3941

Published: Feb. 15, 2023

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and fourth leading cause cancer-related death globally. Tumor cells recruit remodel various types stromal inflammatory to form a tumor microenvironment (TME), which encompasses cellular molecular entities, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), neutrophils (TANs), immune cells, myeloid-derived suppressor (MDSCs), checkpoint molecules cytokines that promote cancer cell growth, as well their drug resistance. HCC usually arises in context cirrhosis, always associated with an enrichment activated are owed chronic inflammation. CAFs major component TME, providing physical support it secreting proteins, such extracellular matrices (ECMs), hepatocyte growth factor (HGF), insulin-like 1/2 (ILGF1/2) can modulate survival. As such, CAF-derived signaling may increase pool resistant thus reducing duration clinical responses increasing degree heterogeneity within tumors. Although often implicated be metastasis resistance, several studies have reported significant phenotypic functional heterogeneity, some display antitumor drug-sensitizing properties. Multiple highlighted relevance crosstalk between other influence progression. basic partially revealed emerging roles immunotherapy resistance evasion, better understanding unique functions progression will contribute development more effective molecular-targeted drugs. In this review article, mechanisms involved CAFs, effects on HCC-cell metastasis, outcomes, comprehensively discussed.

Language: Английский

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