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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Tumor-Associated Macrophage Subsets: Shaping Polarization and Targeting

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7493 - 7493

Published: April 19, 2023

The tumor microenvironment (TME) is a critical regulator of growth, progression, and metastasis. Among the innate immune cells recruited to site, macrophages are most abundant cell population present at all stages progression. They undergo M1/M2 polarization in response signals derived from TME. M1 suppress while their M2 counterparts exert pro-tumoral effects by promoting angiogenesis, metastasis, resistance current therapies. Several subsets phenotype have been observed, often denoted as M2a, M2b, M2c, M2d. These induced different stimuli differ phenotypes well functions. In this review, we discuss key features each subset, implications cancers, highlight strategies that being developed harness TAMs for cancer treatment.

Language: Английский

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Dissecting the treatment-naive ecosystem of human melanoma brain metastasis

Cell, Journal Year: 2022, Volume and Issue: 185(14), P. 2591 - 2608.e30

Published: July 1, 2022

Language: Английский

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Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7910 - 7910

Published: April 26, 2023

Recent advances have greatly improved our understanding of the molecular mechanisms behind atherosclerosis pathogenesis. However, there is still a need to systematize this data from general pathology perspective, particularly with regard atherogenesis patterns in context both canonical and non-classical inflammation types. In review, we analyze various typical phenomena outcomes cellular pro-inflammatory stress atherosclerosis, as well role endothelial dysfunction local systemic manifestations low-grade inflammation. We also present features immune development productive stable unstable plaques, along their similarities differences compared There are numerous factors that act inducers inflammatory process including vascular endothelium aging, metabolic dysfunctions, autoimmune, some cases, infectious damage factors. Life-critical complications such cardiogenic shock severe strokes, associated acute hyperinflammation. Additionally, critical atherosclerotic ischemia lower extremities induces paracoagulation chronic Conversely, sepsis, other conditions, diseases contribute atherogenesis. summary, can be characterized an independent form inflammation, sharing but having fundamental variants (classic vasculitis).

Language: Английский

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Remodeling the tumor microenvironment via blockade of LAIR-1 and TGF-β signaling enables PD-L1–mediated tumor eradication

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(8)

Published: March 1, 2022

Collagens in the extracellular matrix (ECM) provide a physical barrier to tumor immune infiltration, while also acting as ligand for inhibitory receptors. Transforming growth factor-β (TGF-β) is key contributor shaping ECM by stimulating production and remodeling of collagens. TGF-β activation signatures collagen-rich environments have both been associated with T cell exclusion lack responses immunotherapy. Here, we describe effect targeting collagens that signal through leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) combination blockade programmed death 1 (PD-L1). This approach remodeled collagenous matrix, enhanced infiltration CD8+ cells, repolarized suppressive macrophage populations, resulting high cure rates long-term tumor-specific protection across murine models colon mammary carcinoma. The results highlight advantage direct components checkpoint therapy.

Language: Английский

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Corticosteroids for COVID-19 Therapy: Potential Implications on Tuberculosis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(7), P. 3773 - 3773

Published: April 6, 2021

On 11 March 2020, the World Health Organization announced Corona Virus Disease-2019 (COVID-19) as a global pandemic, which originated in China. At host level, COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), affects respiratory system, with clinical symptoms ranging from mild to severe or critical illness that often requires hospitalization and oxygen support. There is no specific therapy for case any common viral disease except drugs reduce load alleviate inflammatory symptoms. Tuberculosis (TB), an infectious Mycobacterium tuberculosis (Mtb), also primarily lungs has signs similar pulmonary SARS-CoV-2 infection. Active TB leading killer among diseases adds burden of COVID-19 pandemic worldwide. In immunocompetent individuals, primary Mtb infection can lead non-progressive, asymptomatic latency. However, latent (LTBI) reactivate symptomatic upon immune-suppressing conditions. Importantly, diagnosis treatment are hampered admixed control measures. The US-Center Disease Control (US-CDC) recommends using antiviral drugs, Remdesivir corticosteroid (CST), such dexamethasone either alone in-combination recommendations patients requiring CSTs cause immunosuppression, besides their anti-inflammatory properties. altered immunity during combined CST therapy, poses significant risk new secondary infections and/or reactivation existing quiescent infections, LTBI. This review highlights various types mechanisms action CSTs, deadly combination two TB. It discusses importance screening LTBI prevent COVID-19.

Language: Английский

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TIGIT blockade repolarizes AML-associated TIGIT⁺M2 macrophages to an M1 phenotype and increases CD47-mediated phagocytosis

Journal for ImmunoTherapy of Cancer, Journal Year: 2022, Volume and Issue: 10(12), P. e004794 - e004794

Published: Dec. 1, 2022

Background Leukemia-associated macrophages (LAMs) represent an important cell population within the tumor microenvironment, but little is known about phenotype, function, and plasticity of these cells. The present study provides extensive characterization in patients with acute myeloid leukemia (AML). Methods phenotype expression coregulatory markers were assessed on bone marrow (BM)-derived LAM populations, using multiparametric flow cytometry. BM blood aspirates obtained from newly diagnosed (pAML, n=59), long-term remission (lrAML, n=8), relapsed (rAML, n=7) monocyte-derived healthy donors (HD, n=17). subpopulations correlated clinical parameters. Using a blocking anti-T-cell immunoreceptor Ig ITIM domains (TIGIT) antibody or mouse IgG2α isotype control, we investigated polarization, secretion cytokines, phagocytosis LAMs vitro. Results In pAML rAML, M1 reduced predominant macrophage consisted immunosuppressive M2 defined by CD163, CD204, CD206, CD86. active AML highly expressed inhibitory receptors such as TIGIT, T-cell immunoglobulin mucin-domain containing-3 protein (TIM-3), lymphocyte-activation gene 3 (LAG-3). High CD163 was associated poor overall survival (OS). addition, increased frequencies TIGIT + intermediate adverse risk according to European Leukemia Network criteria FLT3 ITD mutation. vitro blockade shifted polarization primary peripheral blood-derived toward M1-associated cytokines chemokines. Moreover, augmented anti-CD47-mediated lines Conclusion Our findings suggest that can be redirected into efficient effector may direct relevance near future.

Language: Английский

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An omic and multidimensional spatial atlas from serial biopsies of an evolving metastatic breast cancer

Cell Reports Medicine, Journal Year: 2022, Volume and Issue: 3(2), P. 100525 - 100525

Published: Feb. 1, 2022

Mechanisms of therapeutic resistance and vulnerability evolve in metastatic cancers as tumor cells extrinsic microenvironmental influences change during treatment. To support the development methods for identifying these mechanisms individual people, here we present an omic multidimensional spatial (OMS) atlas generated from four serial biopsies with breast cancer 3.5 years therapy. This resource links detailed, longitudinal clinical metadata that includes treatment times doses, anatomic imaging, blood-based response measurements to exploratory analyses, which comprehensive DNA, RNA, protein profiles; images multiplexed immunostaining; 2- 3-dimensional scanning electron micrographs. These data report aspects heterogeneity evolution genome, signaling pathways, immune microenvironment, cellular composition organization, ultrastructure. We illustrative examples how integrative analyses reveal potential suggest novel vulnerabilities.

Language: Английский

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Glucocorticoid regulation of cancer development and progression

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

Published: April 18, 2023

Glucocorticoids are steroid hormones that regulate a host of cellular and physiological functions. However, they arguably best known for their potent anti-inflammatory properties. Chronic inflammation is well-known to promote the development progression numerous types cancer, emerging evidence suggests glucocorticoid regulation affects cancer development. timing, intensity, duration signaling have important but often contradictory effects on Moreover, glucocorticoids widely used in parallel with radiation chemotherapy control pain, dyspnea, swelling, use may compromise anti-tumor immunity. This review will explore particular focus pro

Language: Английский

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CD163+ macrophages monitor enhanced permeability at the blood–dorsal root ganglion barrier

The Journal of Experimental Medicine, Journal Year: 2023, Volume and Issue: 221(2)

Published: Dec. 20, 2023

In dorsal root ganglia (DRG), macrophages reside close to sensory neurons and have largely been explored in the context of pain, nerve injury, repair. However, we discovered that most DRG interact with monitor vasculature by sampling macromolecules from blood. Characterization revealed a specialized endothelial bed transformed molecular, structural, permeability properties along arteriovenous axis was covered macrophage-interacting pericytes fibroblasts. Macrophage phagocytosis spatially aligned peak permeability, process regulated enhanced caveolar transcytosis cells. Profiling immune landscape two subsets perivascular distinct transcriptome, turnover, function. CD163+ self-maintained locally, specifically participated monitoring, displayed responses during peripheral inflammation, were conserved mouse man. Our work provides molecular explanation for blood-DRG barrier identifies an unappreciated role as integral components DRG-neurovascular unit.

Language: Английский

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