Macrophage Polarization and Its Role in Liver Disease

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 14, 2021

Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity polarization. Under pathological conditions, addition to the resident macrophages, other macrophages also recruited diseased tissues, polarize various phenotypes (mainly M1 M2) under stimulation of factors microenvironment, thus playing different roles functions. Liver diseases hepatic changes caused by a variety pathogenic (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic disease, metabolic-associated fatty fibrosis, hepatocellular carcinoma. Recent studies shown that macrophage polarization plays an role initiation development diseases. However, because both pathogenesis complex, mechanism need be further clarified. Therefore, origin mechanisms reviewed first this paper. It is found involves several molecular mechanisms, mainly TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, miRNA signaling pathways. In addition, paper expounds diseases, which aims provide references for research contributing therapeutic strategy ameliorating modulating

Language: Английский

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Immunotherapy: Reshape the Tumor Immune Microenvironment

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

Published: July 6, 2022

Tumor immune microenvironment (TIME) include tumor cells, cytokines, etc. The interactions between these components, which are divided into anti-tumor and pro-tumor, determine the trend of immunity. Although system can eliminate through cancer-immune cycle, tumors appear to eventually evade from surveillance by shaping an immunosuppressive microenvironment. Immunotherapy reshapes TIME restores killing ability cells. Herein, we review function cells within discuss contribution current mainstream immunotherapeutic approaches remolding TIME. Changes in different forms under intervention immunotherapy shed light on better combination treatment strategies.

Language: Английский

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Lipid-Associated Macrophages Are Induced by Cancer-Associated Fibroblasts and Mediate Immune Suppression in Breast Cancer

Cancer Research, Journal Year: 2022, Volume and Issue: 82(18), P. 3291 - 3306

Published: July 21, 2022

Abstract Tumor-associated macrophages (TAM) play a detrimental role in triple-negative breast cancer (TNBC). In-depth analysis of TAM characteristics and interactions with stromal cells, such as cancer-associated fibroblast (CAF), could provide important biological therapeutic insights. Here we identify at the single-cell level monocyte-derived STAB1+TREM2high lipid-associated macrophage (LAM) subpopulation immune suppressive capacities that is expanded patients resistant to checkpoint blockade (ICB). Genetic depletion this LAM subset mice suppressed TNBC tumor growth. Flow cytometry bulk RNA sequencing data demonstrated coculture TNBC-derived CAFs led reprogramming blood monocytes towards LAMs, which inhibit T-cell activation proliferation. Cell-to-cell interaction modeling assays vitro inflammatory CXCL12–CXCR4 axis CAF–myeloid cell cross-talk recruitment sites. Altogether, these suggest an inflammation model whereby recruited via CAF-driven acquire protumorigenic support immunosuppressive microenvironment. Significance: This work identifies novel lipid–associated functions, offering new leads for interventions cancer.

Language: Английский

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Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

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

Published: Oct. 2, 2023

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as pivotal component tumor microenvironment. The versatility sophisticated mechanisms CAFs in facilitating progression been elucidated extensively, including promoting angiogenesis metastasis, inducing drug resistance, reshaping extracellular matrix, developing an immunosuppressive Owing to their robust tumor-promoting function, are considered promising target for oncotherapy. However, highly heterogeneous group cells. Some subpopulations exert inhibitory role growth, which implies that CAF-targeting approaches must be more precise individualized. This review comprehensively summarize origin, phenotypical, functional heterogeneity CAFs. More importantly, we underscore advances strategies clinical trials CAF various cancers, also progressions immunotherapy.

Language: Английский

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CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: July 14, 2021

Cancer associated fibroblasts (CAFs) and tumor macrophages (TAMs) are among the most important abundant players of microenvironment. CAFs as well TAMs known to play pivotal supportive roles in growth progression. The number CAF or TAM cells is mostly correlated with poor prognosis. Both a reciprocal communication milieu . In addition such interactions, also involved dynamic interrelationship each other. capable altering other’s functions. Here, current understanding distinct mechanisms about complex interplay between summarized. addition, consequences mutual relationship especially for progression immune evasion highlighted, focusing on synergistic pleiotropic effects. crucial components microenvironment; thus, they may prove be potential therapeutic targets. A better tri-directional interactions CAFs, cancer terms will pave way identification novel theranostic cues order target carcinogenesis.

Language: Английский

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Biomaterials tools to modulate the tumour microenvironment in immunotherapy

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 1(2), P. 125 - 138

Published: Jan. 25, 2023

Language: Английский

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Colorectal Cancer‐Derived Small Extracellular Vesicles Promote Tumor Immune Evasion by Upregulating PD‐L1 Expression in Tumor‐Associated Macrophages

Advanced Science, Journal Year: 2022, Volume and Issue: 9(9)

Published: Jan. 17, 2022

Tumor-associated macrophages (TAMs) are one of the most abundant cell types in colorectal cancer (CRC) tumor microenvironment (TME). Recent studies observed complicated "cross-talks" between cells and TME. However, underlying mechanisms still poorly elucidated. Here, PD-L1 levels very low CRC but highly TAMs, a specific PD-L1+ CD206+ macrophage subpopulation identified, which is induced by associated with poor prognosis. Mechanistic investigations reveal that can secrete small extracellular vesicles (sEVs) taken up induce M2 like polarization expression, resulting increased abundance decreased T activity sEV-derived miR-21-5p miR-200a identified as key signaling molecules mediating regulatory effects on macrophages. Further CRC-derived synergistically induces expression regulating PTEN/AKT SCOS1/STAT1 pathways, CD8+ growth. This study suggests inhibiting secretion sEV-miRNAs from targeting TAMs may serve novel methods for treatment well sensitization method anti-PD-L1 therapy CRC.

Language: Английский

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The multifaceted role of autophagy in cancer

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(13)

Published: May 10, 2022

Language: Английский

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Clinical and translational values of spatial transcriptomics

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: April 1, 2022

Abstract The combination of spatial transcriptomics (ST) and single cell RNA sequencing (scRNA-seq) acts as a pivotal component to bridge the pathological phenomes human tissues with molecular alterations, defining in situ intercellular communications knowledge on spatiotemporal medicine. present article overviews development ST aims evaluate clinical translational values for understanding pathogenesis uncovering disease-specific biomarkers. We compare advantages disadvantages sequencing- imaging-based technologies highlight opportunities challenges ST. also describe bioinformatics tools necessary dissecting patterns gene expression cellular interactions potential applications diseases practice one important issues medicine, including neurology, embryo development, oncology, inflammation. Thus, clear objectives, designs, optimizations sampling procedure protocol, repeatability ST, well simplifications analysis interpretation are key translate from bench clinic.

Language: Английский

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Correlation between PD-1/PD-L1 expression and polarization in tumor-associated macrophages: A key player in tumor immunotherapy

Cytokine & Growth Factor Reviews, Journal Year: 2022, Volume and Issue: 67, P. 49 - 57

Published: July 18, 2022

Tumor immunotherapy, such as PD-1/PD-L1 blockade, has shown promising clinical efficacy in patients with various types of tumors. However, the response to blockade a majority malignancies is limited, indicating an urgent need for deeper understanding mechanisms axis-mediated tumor tolerance. As most abundant immune cells stroma, macrophages display multiple phenotypes and functions stimuli microenvironment. been demonstrated be highly expressed tumor-associated (TAMs), TAM polarization important during progression. In this review, we outline relationship between expression polarizations, summarize involvement M2 TAMs PD-1/PD-L1-mediated T-cell exhaustion, discuss improved approaches overcoming resistance by inducing M2/M1 switching TAMs.

Language: Английский

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