Macrophages in immunoregulation and therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 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.

Language: Английский

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The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: May 24, 2022

Recently, in the field of cancer treatment, paradigm has changed to immunotherapy that activates immune system induce attacks. Among them, checkpoint inhibitors (ICI) are attracting attention as excellent and continuous clinical results. However, it shows not only limitations such efficacy some patients or indications, but also side-effects resistance occur. Therefore, is necessary understand factors tumor microenvironment (TME) affect immunotherapy, is, mechanism by which grows while evading suppressing attacks from within TME. Tumors can evade through various mechanisms restricting antigen recognition, inhibiting system, inducing T cell exhaustion. In addition, tumors inhibit accumulating specific metabolites signal TME limiting nutrients available cells. order overcome develop effective treatments therapeutic strategies, an approach needed functions cells integrated manner based on this review, we will examine effects cells, especially how anti-cancer strategies

Language: Английский

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Metabolism of tissue macrophages in homeostasis and pathology

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 19(3), P. 384 - 408

Published: Dec. 7, 2021

Abstract Cellular metabolism orchestrates the intricate use of tissue fuels for catabolism and anabolism to generate cellular energy structural components. The emerging field immunometabolism highlights importance maintenance activities immune cells. Macrophages are embryo- or adult bone marrow-derived leukocytes that key healthy homeostasis but can also contribute pathologies such as metabolic syndrome, atherosclerosis, fibrosis cancer. Macrophage has largely been studied in vitro. However, different organs contain diverse macrophage populations specialize distinct often tissue-specific functions. This context specificity creates diverging challenges fulfill their homeostatic roles particular microenvironment conditions response pathological conditions. Here, we outline current knowledge on requirements adaptations macrophages located tissues during selected diseases.

Language: Английский

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M1/M2 macrophages and their overlaps – myth or reality?

Clinical Science, Journal Year: 2023, Volume and Issue: 137(15), P. 1067 - 1093

Published: Aug. 1, 2023

Abstract Macrophages represent heterogeneous cell population with important roles in defence mechanisms and homoeostasis. Tissue macrophages from diverse anatomical locations adopt distinct activation states. M1 M2 are two polarized forms of mononuclear phagocyte vitro differentiation phenotypic patterns functional properties, but vivo, there is a wide range different macrophage phenotypes between depending on the microenvironment natural signals they receive. In human infections, pathogens use strategies to combat these include shaping polarization towards one or another phenotype. infiltrating tumours can affect patient’s prognosis. have been shown promote tumour growth, while provide both tumour-promoting anti-tumour properties. autoimmune diseases, prolonged activation, as well altered function contribute their onset activity. atherosclerotic lesions, expressing profiles detected potential factors affecting occurrence cardiovascular diseases. allergic inflammation, T2 cytokines drive profiles, which airway inflammation remodelling. transplantations seem acute rejection, fibrosis graft. The view pro-inflammatory suppressing seems be an oversimplification because cells exploit very high level plasticity large scale immunophenotypes overlapping this respect, it would more precise describe M1-like M2-like.

Language: Английский

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Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers

Cancers, Journal Year: 2022, Volume and Issue: 14(7), P. 1681 - 1681

Published: March 25, 2022

Our body is constantly exposed to pathogens or external threats, but with the immune response that our can develop, we fight off and defeat possible attacks infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as existence of a tumour also cause system (IS) be put on alert. Indeed, link between immunology cancer evident these days, IS being used one important targets for treating cancer. able eliminate those abnormal damaged cells found in body, preventing uncontrolled proliferation lead However, several cases, escape IS. It has been observed cells, extracellular matrix, blood vessels, fat various molecules could support growth development. Thus, developing receives structural support, irrigation energy, among other resources, making its survival progression possible. All components accompany help survive grow are called microenvironment (TME). Given importance presence development process, review will focus TME: cells. Immune anti-tumour protecting us against cells; nevertheless, they behave pro-tumoural thus promoting survival. In review, pro-tumour immunity discussed. addition, TME influence dual effect analysed.

Language: Английский

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Nanocomplex‐Mediated In Vivo Programming to Chimeric Antigen Receptor‐M1 Macrophages for Cancer Therapy

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(43)

Published: Sept. 12, 2021

Abstract Chimeric antigen receptor‐T (CAR‐T) cell immunotherapy has shown impressive clinical outcomes for hematologic malignancies. However, its broader applications are challenged due to complex ex vivo cell‐manufacturing procedures and low therapeutic efficacy against solid tumors. The limited effects partially CAR‐T infiltration tumors inactivation of cells by the immunosuppressive tumor microenvironment. Here, a facile approach is presented in program macrophages, which can intrinsically penetrate tumors, into CAR‐M1 macrophages displaying enhanced cancer‐directed phagocytosis anti‐tumor activity. In injected nanocomplexes macrophage‐targeting nanocarriers CAR‐interferon‐γ‐encoding plasmid DNA induce that capable CAR‐mediated cancer phagocytosis, immunomodulation, inhibition growth. Together, this study describes an off‐the‐shelf CAR‐macrophage therapy effective avoids costly processes CAR‐cell manufacturing.

Language: Английский

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Next-Generation CAR T-cell Therapies

Cancer Discovery, Journal Year: 2022, Volume and Issue: 12(7), P. 1625 - 1633

Published: April 12, 2022

Summary: CD19- and B-cell maturation antigen (BCMA)–directed chimeric receptor (CAR) T cells have enabled unprecedented responses in a subset of refractory patients with plasma cell malignancies, leading to their approval by the FDA for treatment leukemia, lymphoma, myeloma. These “living drugs” can become part synthetic immune system, persisting at least decade some patients. However, despite this tremendous impact, significant unmet needs remain hematologic malignancies solid cancers. In perspective, we highlight recent innovations that advance field toward production more potent universal cellular immunotherapy future. Next-generation CAR will incorporate advances gene engineering biology enhance functionality persistence, reduce treatment-associated toxicities. The combination autologous various allogeneic strategies designed target immunosuppressive tumor microenvironment broaden impact future T-cell therapies.

Language: Английский

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Harnessing anti‐tumor and tumor‐tropism functions of macrophages via nanotechnology for tumor immunotherapy

Exploration, Journal Year: 2022, Volume and Issue: 2(3)

Published: Feb. 25, 2022

Reprogramming the immunosuppressive tumor microenvironment by modulating macrophages holds great promise in immunotherapy. As a class of professional phagocytes and antigen-presenting cells innate immune system, can not only directly engulf clear cells, but also play roles presenting tumor-specific antigen to initiate adaptive immunity. However, tumor-associated (TAMs) usually display tumor-supportive M2 phenotype rather than anti-tumor M1 phenotype. They support escape immunological surveillance, aggravate progression, impede T cell Although many TAMs-modulating agents have shown success therapy multiple tumors, they face enormous challenges including poor accumulation off-target side effects. An alternative solution is use advanced nanostructures, which deliver augment therapeutic efficacy, serve as modulators TAMs. Another important strategy exploitation macrophage-derived components tumor-targeting delivery vehicles. Herein, we summarize recent advances targeting engineering for immunotherapy, (1) direct indirect effects on augmentation immunotherapy (2) strategies macrophage-based drug carriers. The existing perspectives immunotherapies are highlighted.

Language: Английский

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Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(11), P. 1351 - 1366

Published: Nov. 21, 2022

Radiation therapy is a mainstay of cancer treatment but does not always lead to complete tumor regression. Here we combine radiotherapy with blockade the 'don't-eat-me' cell-surface molecule CD47 in small cell lung (SCLC), highly metastatic form cancer. potently enhances local antitumor effects preclinical models SCLC. Notably, also stimulates off-target 'abscopal' inhibiting non-irradiated SCLC tumors mice receiving radiation. These abscopal are independent T cells require macrophages that migrate into sites response inflammatory signals produced by radiation and locally activated phagocytose cells. Similar were observed other treated blockade. The systemic activation following may be particularly important patients who suffer from disease.

Language: Английский

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Extracellular‐Vesicle‐Based Drug Delivery Systems for Enhanced Antitumor Therapies through Modulating the Cancer‐Immunity Cycle

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(52)

Published: June 21, 2022

Although immunotherapy harnessing activity of the immune system against tumors has made great progress, treatment efficacy remains limited in most cancers. Current anticancer is primarily based on T-cell-mediated cellular immunity, which highly relies efficiency triggering cancer-immunity cycle, namely, tumor antigen release, presentation by presenting cells, T cell activation, recruitment and infiltration cells into tumors, recognition killing cells. Unfortunately, these immunotherapies are restricted inefficient drug delivery acting only a single step cycle. Due to high biocompatibility, low immunogenicity, intrinsic targeting, easy chemical genetic manipulation, extracellular vesicle (EV)-based systems widely used amplify responses serving as an integrated platform for multiple drugs or therapeutic strategies synergistically activate several steps This review summarizes various mechanisms related affecting cycle disorders. Meanwhile, preparation application EV-based modulating introduced, especially improvement tumors. Finally, opportunities challenges translational clinical applications briefly discussed.

Language: Английский

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