The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth

Cancer Cell, Год журнала: 2023, Номер 41(3), С. 374 - 403

Опубликована: Март 1, 2023

Язык: Английский

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Macrophages in immunoregulation and therapeutics

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 22, 2023

Abstract Macrophages exist in various tissues, several body cavities, and around mucosal surfaces are a vital part of the innate immune system for host defense against many pathogens cancers. possess binary M1/M2 macrophage polarization settings, which perform central role an array tasks via intrinsic signal cascades and, therefore, must be precisely regulated. Many crucial questions about signaling modulation yet to uncovered. In addition, clinical importance tumor-associated macrophages is becoming more widely recognized as significant progress has been made understanding their biology. Moreover, they integral tumor microenvironment, playing regulation wide variety processes including angiogenesis, extracellular matrix transformation, cancer cell proliferation, metastasis, immunosuppression, resistance chemotherapeutic checkpoint blockade immunotherapies. Herein, we discuss signaling, mechanical stresses modulation, metabolic pathways, mitochondrial transcriptional, epigenetic regulation. Furthermore, have broadly extended traps essential roles autophagy aging regulating functions. discussed recent advances macrophages-mediated autoimmune diseases tumorigenesis. Lastly, targeted therapy portray prospective targets therapeutic strategies health diseases.

Язык: Английский

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NF-κB in biology and targeted therapy: new insights and translational implications

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

Опубликована: Март 4, 2024

Abstract NF-κB signaling has been discovered for nearly 40 years. Initially, was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have that its role can be expanded to variety of mechanisms, biological processes, human diseases, treatment options. In this review, we first scrutinize the research process signaling, summarize composition, activation, regulatory mechanism signaling. We investigate interaction other important pathways, including PI3K/AKT, MAPK, JAK-STAT, TGF-β, Wnt, Notch, Hedgehog, TLR The physiological pathological states well intricate involvement inflammation, immune regulation, tumor microenvironment, are also explicated. Additionally, illustrate how is involved cancers, autoimmune cardiovascular metabolic neurological COVID-19. Further, discuss therapeutic approaches targeting IKK inhibitors, monoclonal antibodies, proteasome nuclear translocation DNA binding TKIs, non-coding RNAs, immunotherapy, CAR-T. Finally, provide an outlook field hope present stereoscopic, comprehensive will inform future clinical practice.

Язык: Английский

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The cancer-immunity cycle: Indication, genotype, and immunotype

Immunity, Год журнала: 2023, Номер 56(10), С. 2188 - 2205

Опубликована: Окт. 1, 2023

The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes iterative nature response where killing tumor cells by T initiates subsequent rounds antigen presentation and cell stimulation, maintaining active immunity adapting it evolution. Any step can become rate-limiting, rendering system unable control growth. Here, we update based on remarkable progress past decade. Understanding mechanism checkpoint inhibition has evolved, as our view dendritic in sustaining anti-tumor immunity. We additionally account for role microenvironment facilitating, not just suppressing, response, discuss importance considering tumor's immunological phenotype, "immunotype". While these new insights add some complexity cycle, they also provide targets research therapeutic intervention.

Язык: Английский

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A timeline of tumour-associated macrophage biology

Nature reviews. Cancer, Год журнала: 2023, Номер 23(4), С. 238 - 257

Опубликована: Фев. 15, 2023

Язык: Английский

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CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers

Science, Год журнала: 2023, Номер 381(6657), С. 515 - 524

Опубликована: Авг. 3, 2023

Tumor microenvironments (TMEs) influence cancer progression but are complex and often differ between patients. Considering that microenvironment variations may reveal rules governing intratumoral cellular programs disease outcome, we focused on tumor-to-tumor variation to examine 52 head neck squamous cell carcinomas. We found macrophage polarity-defined by

Язык: Английский

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Applications of single-cell RNA sequencing in drug discovery and development

Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(6), С. 496 - 520

Опубликована: Апрель 28, 2023

Single-cell technologies, particularly single-cell RNA sequencing (scRNA-seq) methods, together with associated computational tools and the growing availability of public data resources, are transforming drug discovery development. New opportunities emerging in target identification owing to improved disease understanding through cell subtyping, highly multiplexed functional genomics screens incorporating scRNA-seq enhancing credentialling prioritization. ScRNA-seq is also aiding selection relevant preclinical models providing new insights into mechanisms action. In clinical development, can inform decision-making via biomarker for patient stratification more precise monitoring response progression. Here, we illustrate how methods being applied key steps discuss ongoing challenges their implementation pharmaceutical industry. There have been significant recent advances development remarkable Ferran colleagues primarily pipeline, from decision-making. Ongoing potential future directions discussed.

Язык: Английский

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Macrophages and microglia in glioblastoma: heterogeneity, plasticity, and therapy

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(1)

Опубликована: Янв. 2, 2023

Glioblastoma (GBM) is the most aggressive tumor in central nervous system and contains a highly immunosuppressive microenvironment (TME). Tumor-associated macrophages microglia (TAMs) are dominant population of immune cells GBM TME that contribute to hallmarks, including immunosuppression. The understanding TAMs has been limited by lack powerful tools characterize them. However, recent progress on single-cell technologies offers an opportunity precisely at level identify new TAM subpopulations with specific tumor-modulatory functions GBM. In this Review, we discuss heterogeneity plasticity summarize current TAM-targeted therapeutic potential We anticipate use followed functional studies will accelerate development novel effective therapeutics for patients.

Язык: Английский

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Macrophages at the interface of the co-evolving cancer ecosystem

Cell, Год журнала: 2023, Номер 186(8), С. 1627 - 1651

Опубликована: Март 15, 2023

Язык: Английский

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Metabolism, metabolites, and macrophages in cancer

Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)

Опубликована: Июль 25, 2023

Abstract Tumour-associated macrophages (TAMs) are crucial components of the tumour microenvironment and play a significant role in development drug resistance by creating an immunosuppressive microenvironment. Macrophages essential both innate adaptive immune systems contribute to pathogen regulation organism homeostasis. Macrophage function polarization closely linked altered metabolism. Generally, M1 rely primarily on aerobic glycolysis, whereas M2 depend oxidative Metabolic studies have revealed that metabolic signature TAMs metabolites regulate TAMs. However, precise effects reprogramming tumours remain incompletely understood. In this review, we discuss impact pathways macrophage as well potential strategies for metabolism cancer treatment.

Язык: Английский

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