Tumor‐associated macrophages in liver cancer: From mechanisms to therapy

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(11), P. 1112 - 1140

Published: Sept. 7, 2022

Abstract Multidimensional analyses have demonstrated the presence of a unique tumor microenvironment (TME) in liver cancer. Tumor‐associated macrophages (TAMs) are among most abundant immune cells infiltrating TME and present at all stages cancer progression, targeting TAMs has become one favored immunotherapy strategies. In addition, distinct origins. At early stage cancer, can provide niche for maintenance stem cells. contrast, (CSCs) or poorly differentiated key factors modulating macrophage activation. review, we first propose origin connection between precursor Macrophages undergo dynamic phenotypic transition during carcinogenesis. this course such transition, it is critical to determine appropriate timing therapy block specific markers suppress pro‐tumoral TAMs. The review provides more detailed discussion trends surface than previous reviews. Complex crosstalk occurs play indispensable roles angiogenesis, autophagy due their heterogeneity robust plasticity. interact with other by directing cell‐to‐cell contact secreting various effector molecules. Similarly, combined drive recruitment polarization. Despite latest achievements advancements treatment strategies following studies, comprehensive discussions on communication currently lacking. discussed interactions (from cell maturation), therapeutic (including chimeric antigen receptor macrophages), clinical trials hepatocellular carcinoma (HCC) intrahepatic cholangiocarcinoma (iCCA) rationale further investigation as potential target treating patients

Language: Английский

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Exploring treatment options in cancer: Tumor treatment strategies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 17, 2024

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical psychological challenges. Encouragingly, the landscape of tumor treatment has undergone a comprehensive remarkable transformation. Emerging fervently pursued modalities are small molecule targeted agents, antibody-drug conjugates (ADCs), cell-based therapies, gene therapy. These cutting-edge not only afford personalized precise targeting, but also provide enhanced comfort potential to impede disease progression. Nonetheless, it is acknowledged that these strategies still harbour untapped for further advancement. Gaining understanding merits limitations holds promise offering novel perspectives clinical practice foundational research endeavours. In this review, we discussed different modalities, including drugs, peptide antibody cell therapy, It will detailed explanation each method, addressing their status development, challenges, solutions. The aim assist clinicians researchers in gaining deeper diverse options, enabling them carry out effective advance more efficiently.

Language: Английский

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The role of tumor-associated macrophages in tumor immune evasion

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)

Published: May 7, 2024

Abstract Background Tumor growth is closely linked to the activities of various cells in tumor microenvironment (TME), particularly immune cells. During progression, circulating monocytes and macrophages are recruited, altering TME accelerating growth. These adjust their functions response signals from stromal Tumor-associated (TAMs), similar M2 macrophages, key regulators TME. Methods We review origins, characteristics, TAMs within This analysis includes mechanisms through which facilitate evasion promote metastasis. Additionally, we explore potential therapeutic strategies that target TAMs. Results instrumental mediating malignant behaviors. They release cytokines inhibit effector attract additional immunosuppressive primarily T cells, inducing exhaustion directly, influencing activity indirectly cellular interactions, or suppressing checkpoints. directly involved proliferation, angiogenesis, invasion, Summary Developing innovative tumor-targeted therapies immunotherapeutic currently a promising focus oncology. Given pivotal role evasion, several approaches have been devised them. include leveraging epigenetics, metabolic reprogramming, engineering repolarize TAMs, inhibiting recruitment activity, using as drug delivery vehicles. Although some these remain distant clinical application, believe future targeting will offer significant benefits cancer patients.

Language: Английский

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Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives

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

Published: April 29, 2024

Abstract Hepatocellular carcinoma (HCC) is a major health concern worldwide, with limited therapeutic options and poor prognosis. In recent years, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in the systemic treatment of HCC. The combination treatments based on ICIs been trend this area. Recently, dual blockade durvalumab plus tremelimumab has also emerged an effective for advanced However, majority HCC patients obtain benefits. Understanding immunological rationale exploring novel ways to improve efficacy immunotherapy drawn much attention. review, we summarize latest area, ongoing clinical trials immune-based therapies, well strategies chimeric antigen receptor T cells, personalized neoantigen vaccines, oncolytic viruses, bispecific antibodies.

Language: Английский

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Hepatocellular carcinoma: signaling pathways, targeted therapy, and immunotherapy

MedComm, Journal Year: 2024, Volume and Issue: 5(2)

Published: Feb. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a high mortality rate. It regarded as significant public health issue because of its complicated pathophysiology, metastasis, and recurrence rates. There are no obvious symptoms in early stage HCC, which often leads to delays diagnosis. Traditional treatment methods such surgical resection, radiotherapy, chemotherapy, interventional therapies have limited therapeutic effects for HCC patients or metastasis. With development molecular biology immunology, signaling pathways immune checkpoint were identified main mechanism progression. Targeting these molecules has become new direction HCC. At present, combination targeted drugs inhibitors first choice advanced patients. In this review, we mainly focus on cutting‐edge research corresponding therapy immunotherapy great significance comprehensively understand pathogenesis search potential targets, optimize strategies

Language: Английский

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Decoding the spatiotemporal heterogeneity of tumor-associated macrophages

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: July 27, 2024

Abstract Tumor-associated macrophages (TAMs) are pivotal in cancer progression, influencing tumor growth, angiogenesis, and immune evasion. This review explores the spatial temporal heterogeneity of TAMs within microenvironment (TME), highlighting their diverse subtypes, origins, functions. Advanced technologies such as single-cell sequencing multi-omics have elucidated intricate interactions between other TME components, revealing mechanisms behind recruitment, polarization, distribution. Key findings demonstrate that support vascularization, promote epithelial-mesenchymal transition (EMT), modulate extracellular matrix (ECM) remodeling, etc., thereby enhancing invasiveness metastasis. Understanding these complex dynamics offers new therapeutic targets for disrupting TAM-mediated pathways overcoming drug resistance. underscores potential targeting to develop innovative therapies, emphasizing need further research into characteristics functional roles TME.

Language: Английский

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The strategies to cure cancer patients by eradicating cancer stem-like cells

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 18, 2023

Abstract Cancer stem-like cells (CSCs), a subpopulation of cancer cells, possess remarkable capability in proliferation, self-renewal, and differentiation. Their presence is recognized as crucial factor contributing to tumor progression metastasis. CSCs have garnered significant attention therapeutic focus an etiologic root treatment-resistant cells. Increasing evidence indicated that specific biomarkers, aberrant activated pathways, immunosuppressive microenvironment (TME), immunoevasion are considered the culprits occurrence maintenance properties including multi-directional Targeting CSC stemness-associated TME, inducing differentiation improve eradication and, therefore, treatment. This review comprehensively summarized these targeted therapies, along with their current status clinical trials. By exploring implementing strategies aimed at eradicating CSCs, researchers aim treatment outcomes overcome challenges posed by CSC-mediated therapy resistance.

Language: Английский

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The NR_109/FUBP1/c-Myc axis regulates TAM polarization and remodels the tumor microenvironment to promote cancer development

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(5), P. e006230 - e006230

Published: May 1, 2023

Background Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and exert an important role in progression. Due to heterogeneity plasticity TAMs, modulating polarization states TAMs is considered as potential therapeutic strategy for tumors. Long noncoding RNAs (lncRNAs) have been implicated various physiological pathological processes, yet underlying mechanism on how lncRNAs manipulate still unclear remains be further investigated. Methods Microarray analyses were employed characterize lncRNA profile involved THP-1-induced M0, M1 M2-like macrophage. Among those differentially expressed lncRNAs, NR_109 was studied, its function macrophage effects condition medium or mediated by proliferation, metastasis TME remodeling both vitro vivo. Moreover, we revealed interacted with far upstream element-binding protein 1 (FUBP1) regulate stability through hindering ubiquitination modification competitively binding JVT-1. Finally, examined sections patients probe correlation among expression related proteins, showing clinical significance NR_109. Results We found that highly macrophages. Knockdown impeded IL-4 induced significantly reduced activity support proliferation cells Mechanistically, competed JVT-1 bind FUBP1 at C-terminus domain, ubiquitin-mediated degradation FUBP1, activated c-Myc transcription thus promoted polarization. Meanwhile, factor, could promoter enhance Clinically, high CD163 + from tissues positively correlated poor stages gastric cancer breast cancer. Conclusions Our work first time exerted crucial regulating phenotype-remodeling via NR_109/FUBP1/c-Myc positive feedback loop. Thus, has great translational potentials diagnosis, prognosis immunotherapy

Language: Английский

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SPP1 represents a therapeutic target that promotes the progression of oesophageal squamous cell carcinoma by driving M2 macrophage infiltration

British Journal of Cancer, Journal Year: 2024, Volume and Issue: 130(11), P. 1770 - 1782

Published: April 10, 2024

Language: Английский

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Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(1), P. e008094 - e008094

Published: Jan. 1, 2024

Background Hepatocellular carcinoma (HCC) is an exceptionally immunosuppressive malignancy characterized by limited treatment options and a dismal prognosis. Macrophages constitute the primary heterogeneous immune cell population within HCC microenvironment. Our objective to identify distinct subsets of macrophages implicated in progression their resistance immunotherapy. Methods Intratumoral macrophage-specific marker genes were identified via single-cell RNA sequencing analyses. The clinical relevance phospholipase A2 Group VII (PLA2G7), pivotal enzyme phospholipid metabolism, was assessed patients with through immunohistochemistry immunofluorescence. Flow cytometry vitro co-culture system used elucidate specific role PLA2G7 macrophages. Orthotopic subcutaneous mouse models employed evaluate potential inhibitor complementing checkpoint blockade (ICB) therapy. Results Single-cell analyses disclosed predominant expression intratumoral significantly correlated poorer prognosis immunotherapy HCC. high represent highly subset impede CD8 T-cell activation. Pharmacological inhibition darapladib improved therapeutic efficacy anti-programmed death protein 1 antibodies models. Conclusions Macrophage-specific serves as novel biomarker capable prognosticating responsiveness inhibiting has enhance ICB therapy for

Language: Английский

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