Macrophage morphology correlates with single-cell diversity and prognosis in colorectal liver metastasis

The Journal of Experimental Medicine, Journal Year: 2020, Volume and Issue: 217(11)

Published: Aug. 12, 2020

It has long been known that in vitro polarized macrophages differ morphology. Stemming from a conventional immunohistology observation, we set out to test the hypothesis morphology of tumor-associated (TAMs) colorectal liver metastasis (CLM) represents correlate functional diversity with prognostic significance. Density and morphological metrics TAMs were measured correlated clinicopathological variables. While density did not survival CLM patients, cell area identified small (S-TAM) large (L-TAM) associated 5-yr disease-free rates 27.8% 0.2%, respectively (P < 0.0001). RNA sequencing morphologically distinct LXR/RXR as most enriched pathway macrophages, up-regulation genes involved cholesterol metabolism, scavenger receptors, MERTK, complement. In single-cell analysis mononuclear phagocytes tissues, S-TAM L-TAM signatures differentially individual clusters. These results suggest morphometric characterization can serve simple readout TAM strong

Language: Английский

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Immune cell - produced ROS and their impact on tumor growth and metastasis

Redox Biology, Journal Year: 2021, Volume and Issue: 42, P. 101891 - 101891

Published: Feb. 6, 2021

Reactive oxygen species (ROS) are derivatives of molecular (O2) involved in various physiological and pathological processes. In immune cells, ROS mediators pivotal functions such as phagocytosis, antigen presentation recognition, cytolysis well phenotypical differentiation. Furthermore, exert immunosuppressive effects on T natural killer (NK) cells which is particular importance the so-called "tumor microenvironment" (TME) solid tumors. This term describes heterogenous group non-malignant including tumor-associated fibroblasts vascular bacteria etc. by cancer surrounded with whom they engage functional crosstalk. Importantly, pharmacological targeting TME and, specifically, utilizing checkpoint inhibitors - monoclonal antibodies that mitigate immunosuppression turned out to be a major breakthrough treatment malignant this review, we aim give an overview role produced play during initiation, progression metastatic outgrowth cancers. Finally, summarize findings how could targeted therapeutically increase efficacy immunotherapy discuss factors determining therapeutic success redox modulation

Language: Английский

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Hepatic macrophages: Key players in the development and progression of liver fibrosis

Liver International, Journal Year: 2021, Volume and Issue: 41(10), P. 2279 - 2294

Published: May 9, 2021

Abstract Hepatic fibrosis is a common pathological process involving persistent liver injury with various etiologies and subsequent inflammatory responses that occur in chronic diseases. If left untreated, can progress to cirrhosis, hepatocellular carcinoma eventually, failure. Unfortunately, date, there no effective treatment for fibrosis, the exception of transplantation. Although pathophysiology multifactorial includes activation hepatic stellate cells, which are known drive fibrogenesis, macrophages have emerged as central players development regression. macrophages, consist resident (Kupffer cells) monocyte‐derived been shown play an intricate role initiation injury, progression promotion resolution. These features made uniquely attractive therapeutic targets fight against fibrosis. In this review, we synthesised literature highlight functions regulation heterogeneity macrophages. Furthermore, using existing findings, attempt offer insights into molecular mechanisms underlying phenotypic switch from fibrogenic restorative heterogeneity, modes action A better understanding these may guide novel anti‐fibrotic therapies (eg macrophage subset‐targeted treatments) combat future.

Language: Английский

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Immunological mechanisms of inflammatory diseases caused by gut microbiota dysbiosis: A review

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114985 - 114985

Published: June 11, 2023

The gut microbiota is indispensable for maintaining host health by enhancing the host's digestive capacity, safeguarding intestinal epithelial barrier, and preventing pathogen invasion. Additionally, exhibits a bidirectional interaction with immune system promotes of to mature. Dysbiosis microbiota, primarily caused factors such as genetic susceptibility, age, BMI, diet, drug abuse, significant contributor inflammatory diseases. However, mechanisms underlying diseases resulting from dysbiosis lack systematic categorization. In this study, we summarize normal physiological functions symbiotic in healthy state demonstrate that when occurs due various external factors, are lost, leading pathological damage lining, metabolic disorders, barrier damage. This, turn, triggers disorders eventually causes systems. These discoveries provide fresh perspectives on how diagnose treat unrecognized variables might affect link between illnesses need further studies extensive basic clinical research will still be required investigate relationship future.

Language: Английский

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Macrophage Polarization in Cardiac Tissue Repair Following Myocardial Infarction

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(5), P. 2715 - 2715

Published: March 8, 2021

Cardiovascular disease is the leading cause of mortality and morbidity around globe, creating a substantial socio-economic burden as result. Myocardial infarction significant contributor to detrimental impact cardiovascular disease. The death cardiomyocytes following myocardial causes an immune response which leads further destruction tissue, subsequently, results in formation non-contractile scar tissue. Macrophages have been recognized important regulators participants inflammation fibrosis infarction. are generally classified into two distinct groups, namely, classically activated, or M1 macrophages, alternatively M2 macrophages. phenotypic profile cardiac however, much more diverse should not be reduced these subsets. In this review, we describe phenotypes functions macrophages present healthy, well infarcted heart, analyze them with respect polarization states. Furthermore, discuss therapeutic strategies utilize macrophage towards anti-inflammatory reparative phenotype for treatment

Language: Английский

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