Lipid metabolism reprogramming in tumor-associated macrophages and implications for therapy

Lipids in Health and Disease, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 31, 2023

Abstract The tumormicroenvironment (TME) plays a key role in tumor progression. Tumor-associated macrophages (TAMs), which are natural immune cells abundantin the TME, mainly divided into anti-tumor M1 subtype and pro-tumor M2 subtype. Due to high plasticity of TAMs, conversion phenotype hypoxic hypoglycemic TME promotes cancer progression, is closely related lipid metabolism. Key factors metabolism including peroxisome proliferator-activated receptor lipoxygenase, promote formation immunosuppressive microenvironment facilitate escape. In addition, accumulation causing TAMs polarize phenotype. Moreover, other metabolism, such as abhydrolase domain containing 5 fatty acid binding protein, have both promoting inhibiting effects on cells. Therefore, further research tumors still required. statins, core drugs regulating cholesterol can inhibit rafts adhesion cells, sensitize them chemotherapeutic drugs. Clinical studies simvastatin lovastatin variety underway. This article provides comprehensive review new ideas for targeting therapy.

Language: Английский

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Phagocytosis increases an oxidative metabolic and immune suppressive signature in tumor macrophages

The Journal of Experimental Medicine, Journal Year: 2023, Volume and Issue: 220(6)

Published: March 7, 2023

Phagocytosis is a key macrophage function, but how phagocytosis shapes tumor-associated (TAM) phenotypes and heterogeneity in solid tumors remains unclear. Here, we utilized both syngeneic novel autochthonous lung tumor models which neoplastic cells express the fluorophore tdTomato (tdTom) to identify TAMs that have phagocytosed vivo. Phagocytic tdTompos upregulated antigen presentation anti-inflammatory proteins, downregulated classic proinflammatory effectors compared tdTomneg TAMs. Single-cell transcriptomic profiling identified TAM subset-specific common gene expression changes associated with phagocytosis. We uncover phagocytic signature predominated by oxidative phosphorylation (OXPHOS), ribosomal, metabolic genes, this correlates worse clinical outcome human cancer. Expression of OXPHOS mitochondrial content, functional utilization were increased dendritic also display similar changes. Our identification as distinct myeloid cell state links vivo tumor-promoting phenotypes.

Language: Английский

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Redefining the human corneal immune compartment using dynamic intravital imaging

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(31)

Published: July 24, 2023

The healthy human cornea is a uniquely transparent sensory tissue where immune responses are tightly controlled to preserve vision. contains cells that widely presumed be intraepithelial dendritic (DCs). Corneal have diverse cellular morphologies and morphological alterations used as marker of inflammation injury. Based on our imaging corneal T in mice, we hypothesized many commonly defined DCs lymphocytes (IELs). To investigate this, developed functional vivo confocal microscopy (Fun-IVCM) cell dynamics the epithelium stroma. We show resident cells. These IELs characterized by rapid, persistent motility interact with nerves. Imaging deeper into stroma, crawling macrophages rare motile patrol tissue. Furthermore, identify altered behaviors response short-term contact lens wear (acute inflammatory stimulus), well individuals allergy (chronic stimulus) was modulated therapeutic intervention. findings redefine current understanding subsets reveal how respond adapt chronic acute stimuli.

Language: Английский

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High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis

Cancer Immunology Research, Journal Year: 2023, Volume and Issue: 11(4), P. 405 - 420

Published: Jan. 18, 2023

Abstract Patients with colorectal liver metastasis (CLM) present heterogenous clinical outcomes and improved classification is needed to ameliorate the therapeutic output. Macrophages (Mϕ) hold promise as prognostic classifiers targets. Here, stemming from a single-cell analysis of mononuclear phagocytes infiltrating human CLM, we identified two Mϕ markers associated distinct populations opposite relevance. The invasive margin CLM was enriched in pro-inflammatory monocyte-derived (MoMϕ) expressing monocytic marker SERPINB2, more differentiated population, tumor-associated (TAM), glycoprotein nonmetastatic melanoma protein B (GPNMB). SERPINB2+ MoMϕ had an early inflammatory profile, whereas GPNMB+ TAMs were pathways matrix degradation, angiogenesis, lipid metabolism found closer tumor margin, confirmed by spatial transcriptomics on specimens. In cohort patients, high infiltration cells independently longer disease-free survival (DFS; P = 0.033), density correlated shorter DFS (P 0.012) overall 0.002). Cell–cell interaction defined opposing roles for TAMs, suggesting that are discrete may be exploited further translation immune-based stratification tool. This study provides evidence how multi-omics approaches can identify nonredundant, clinically relevant patient tools GPNMB has been shown set immunosuppressive mode. Our dimensional analyses provide negative indicator potential player protumor function populations.

Language: Английский

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Locally sourced: site-specific immune barriers to metastasis

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(8), P. 522 - 538

Published: Feb. 7, 2023

Language: Английский

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