A colorectal liver metastasis prediction model based on the combination of lipoprotein-associated phospholipase A2 and serum biomarker levels

Clinica Chimica Acta, Journal Year: 2025, Volume and Issue: 568, P. 120143 - 120143

Published: Jan. 16, 2025

Language: Английский

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Recruitment of CXCR4+ type 1 innate lymphoid cells distinguishes sarcoidosis from other skin granulomatous diseases

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(17)

Published: Sept. 2, 2024

Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood skin from patients with sarcoid non-sarcoid granulomas, we discovered granulomas different diseases exhibit unique immune cell recruitment molecular signatures. Sarcoid were specifically enriched for type 1 innate lymphoid cells (ILC1s) B exhibited programs associated formation of mature tertiary structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung sarcoidosis also displayed similar recruitment. Thus, granuloma was not generic response. In addition to tissue-specific effects, an 8-fold increase in circulating ILC1s, which correlated treatment status. Multiple types induced signaling sarcoidosis, Th1 T cells, macrophages, ILCs. Mechanistically, CXCR4 inhibition reduced sarcoidosis-activated migration, targeting or total ILCs attenuated noninfectious mouse model. Taken together, our results show ILC1s are tissue biomarker distinguishes other diseases. Repurposing existing inhibitors may offer new this devastating disease.

Language: Английский

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Modulating lipid metabolism improves tumor immunotherapy

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(2), P. e010824 - e010824

Published: Feb. 1, 2025

Immunotherapy has progressed significantly in cancer treatment; however, several factors influence its outcomes. Abnormal lipid metabolism, which is frequently observed cancers, promotes tumor proliferation, invasion, and metastasis. Li et al from the Medical Oncology Department of Chongqing University Cancer Hospital constructed a metabolism scoring system reported that MK1775 inhibited fatty acid oxidation tumor-associated macrophages reduced T-cell infiltration, further enhancing efficacy immunotherapy. This study demonstrated critical role Currently, lipids, such as acids, phospholipids, cholesterol, been to affect microenvironment by regulating immune cells, including T natural killer macrophages. These metabolic changes can impair immunotherapy, resulting progression. Consequently, emerges an important regulator for improving immunotherapeutic outcomes provides novel powerful strategy combination therapy.

Language: Английский

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Development of Fully Human Antibodies Targeting SIRPα and PLA2G7 for Cancer Therapy

Antibodies, Journal Year: 2025, Volume and Issue: 14(1), P. 21 - 21

Published: March 3, 2025

Background: Macrophages play an important role in eliminating diseased and damaged cells through programmed cell death. Signal regulatory protein alpha (SIRPα) is a crucial immune checkpoint primarily expressed on myeloid macrophages. It initiates ‘do not eat me’ signal when engaged with CD47, which typically at elevated levels multiple solid tumors. The phospholipase A2 Group 7 (PLA2G7), mainly secreted by macrophages, interacts oxidized low-density lipoprotein (oxLDL) associates several vascular diseases cancers. Methods: To identify potent fully human monoclonal antibodies (mAbs) against SIRPα PLA2G7, we conducted bio-panning of phage antibody libraries. Results: We isolated one Fab (1B3) VH (1A3) for SIRPα, as well (1H8) (1A9) PLA2G7; the 1B3 1A3 are competitively bound to interfering CD47 binding. IgG VH-Fc augmented macrophage-mediated phagocytic activity combined anti-EGFR antibody, cetuximab. anti-PLA2G7 exhibited high specificity PLA2G7 antigen effectively blocked enzymatic half-maximal inhibitory concentrations (IC50) single-digit nanomolar range. Additionally, 1H8 its derivative bispecific ability block PLA2G7-mediated tumor migration. Conclusions: Our anti-SIRPα mAbs expected serve inhibitors enhancing antitumor responses SIRPα-positive cells. Moreover, our represent promising blockade potential enhance both anti-tumor anti-aging responses. Anti-SIRPα can modulate macrophage inflammatory

Language: Английский

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Metagenomic and transcriptomic investigation of pediatric acute liver failure cases reveals a common pathway predominated by monocytes

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

ABSTRACT In 2022, a cluster of severe childhood hepatitis was detected primarily in Europe and North America, leading to global alert by the World Health Organization. An association with adeno-associated virus 2 (AAV2) conjunction human adenoviruses found. Five percent cases progressed acute liver failure, necessitating transplantation. The mechanism disease that accounts for fulminant failure these patients remains incompletely described. upsurge observed five total presented Dutch national referral center pediatric transplantation spring 2022. in-depth molecular analysis performed using targeted transcriptomics metagenomics identify any present cases, immune profile haplotypes, differentially expressed gene groups. Explanted tissue plasma samples ( n = 15) were subjected viral metagenomic transcriptomic profiling, targeting >600 inflammatory genes. Liver signatures transplanted compared those controls from biobank 6). AAV2, adenoviruses, herpesviruses explant cases. Epstein-Barr varicella zoster infection pathognomonic clinical symptomatology preceded two respective AAV2 one-third control livers. Excessive activation monocyte pathways explants controls. Remarkably, this signature comparable and/or herpesviruses-positive transplant Our multi-omic findings suggest common profile, an upregulation which had similar outcomes. cohort presented, not exclusively associated suggesting other processes may have contributed uniform cascade irreversible pathology. IMPORTANCE Since appearance unknown origin several groups reported high number contrast heterogeneous both species—adenovirus C F—and sequences. mechanisms occurring 5% remain current study adds previous data including during upsurge, enabling analyses inflammation expression profiles different viruses relation This led discovery transcriptome

Language: Английский

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PLA2G7 promotes immune evasion of bladder cancer through the JAK-STAT-PDL1 axis

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 1, 2025

Language: Английский

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Multi-omics analysis reveals inhibition of osteosarcoma progression by sporoderm-removed Ganoderma lucidum spores via targeting glycerophospholipid and fatty acid Metabolism

Published: April 30, 2025

Osteosarcoma (OS) is a severe malignancy affecting children and adolescents, with limited effective treatments leading to poor outcomes. This study explored the potential of sporoderm-removed Ganoderma lucidum spores (RGLS) as novel therapeutic agent against OS elucidated its mechanism action. Our in vivo vitro experiments showed that RGLS significantly inhibited S-180 cell proliferation, colony formation, migration, while simultaneously inducing apoptosis. Multi-omics analysis revealed disrupted glycerophospholipid metabolism by upregulating lysophosphatidylcholine (LysoPC) levels through phospholipase A2 (PLA2)-mediated pathways. Co-culture assays further demonstrated promoted endocytosis macrophage-derived Pla2g7 protein into cells, enhancing anti-cancer effects. Additionally, modulated cellular fatty acid profile suppressed β-oxidation long-chain acids, energy depletion in cells. These findings provide view multi-targeted mechanisms RGLS, positioning it promising candidate for therapy.

Language: Английский

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The Role of Metabolic Reprogramming in the Tumor Immune Microenvironment: Mechanisms and Opportunities for Immunotherapy in Hepatocellular Carcinoma

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5584 - 5584

Published: May 21, 2024

As one of the emerging hallmarks tumorigenesis and tumor progression, metabolic remodeling is common in microenvironment. Hepatocellular carcinoma (HCC) third leading cause global tumor-related mortality, causing a series alterations response to nutrient availability consumption fulfill demands biosynthesis carcinogenesis. Despite efficacy immunotherapy treating HCC, rate remains unsatisfactory. Recently, research has focused on reprogramming its effects immune state microenvironment, rate. In this review, we delineate observed HCC influence We discuss strategies aimed at enhancing rates overcoming resistance through interventions, focusing targeting glucose, lipid, or amino acid metabolism, as well systemic regulation.

Language: Английский

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Co-inhibition of TGF-β and PD-L1 pathways in a metastatic colorectal cancer mouse model triggers interferon responses, innate cells and T cells, alongside metabolic changes and tumor resistance

OncoImmunology, Journal Year: 2024, Volume and Issue: 13(1)

Published: March 20, 2024

Colorectal cancer (CRC) is the third most prevalent worldwide with a high mortality rate (20-30%), especially due to metastasis adjacent organs. Clinical responses chemotherapy, radiation, targeted and immunotherapies are limited subset of patients making metastatic CRC (mCRC) difficult treat. To understand therapeutic modulation immune response in mCRC, we have used genetically engineered mouse model (GEMM), "KPN", which resembles human 'CMS4'-like subtype. We show here that transforming growth factor (TGF-β1), secreted by KPN organoids, increases cell proliferation, inhibits splenocyte activation

Language: Английский

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Dynamics of Liver Cancer Cellular Taxa Revealed Through Single-cell RNA Sequencing: advances and challenges

Cancer Letters, Journal Year: 2024, Volume and Issue: unknown, P. 217394 - 217394

Published: Dec. 1, 2024

Language: Английский

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