Mechanisms of TREM2 mediated immunosuppression and regulation of cancer progression

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: April 25, 2024

Cancer immunotherapy has recently emerged as a key strategy for cancer treatment. TREM2, target regulating the tumor immune microenvironment, is important in treatment and progression. TREM2 an signaling hub that regulates multiple pathological pathways. It not only suppresses anti-tumor responses by inhibiting T cell-mediated responses, but it also influences tumorigenesis affecting NK immunity. Noticeably, expression levels vary significantly among different cells, can regulate progression modulating various Above all, summarizing role of mechanism which progression, this paper clarifies TREM2’s both therapy, identifying new therapeutic oncology diseases.

Language: Английский

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Large Peritoneal Macrophages Play No Role in the Pathogenesis of Postoperative Ileus Induced by Intestinal Manipulation

Neurogastroenterology & Motility, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

ABSTRACT Introduction Postoperative ileus (POI) is an iatrogenic disorder marked by temporary impaired gastrointestinal (GI) motility post‐abdominal surgery. Surgical handling of the intestine activates resident macrophages (Mfs), leading to inflammatory cytokine release and leukocyte recruitment into muscularis , which compromises intestinal contractility. The mechanisms behind this activation are unclear. Recent studies suggest peritoneal Mfs, particularly large (LPMs), might play a role in sterile inflammation rapidly recruiting serosal layer gut aiding tissue damage resolution. Methods To identify immune cells involved early phase POI, single‐cell RNA sequencing (scRNA‐seq) was conducted. migration LPMs post‐surgery studied using adoptive transfer techniques. were depleted via intraperitoneal injection clodronate liposomes. Subsequently, flow cytometry, quantitative PCR (qPCR), immunofluorescence performed assess impact LPM depletion analyze cell populations effects. Results (1) Intestinal manipulation (IM) leads accumulation monocytes, neutrophils, mature CD8+ T cells, within 2 h post‐surgery. (2) Heparin treatment does not affect transit or reduce IL‐6, IL‐1a, IL‐1b expression POI. (3) Depletion liposome prevent monocyte, neutrophil, Mfs infiltration externa nor it improve expression. (4) migrate serosa after IM but do enter . Conclusion Inferences adhere following participate response delayed transit. Consequently, pathogenesis

Language: Английский

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PerC B‐Cells Activation via Thermogenetics‐Based CXCL12 Generator for Intraperitoneal Immunity Against Metastatic Disseminated Tumor Cells

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 26, 2025

Abstract During cancer peritoneal metastasis (PM), conventional antigen‐presenting cells (dendritic cells, macrophages) promote tumorigenesis and immunosuppression in cavity. While intraperitoneal immunotherapy (IPIT) has been used clinical investigations to relieve PM, the limited knowledge of immunocytes hindered development therapeutic IPIT. Here, a dendritic cell‐independent, next‐generation IPIT is described that activates cavity B (PerC B) cell subsets for anti‐tumor immunity via exogenous antigen presentation. The PerC B‐cell‐involved framework consists an isotropic‐porous, cell‐fitting, thermogenetics‐based CXCL12 generator. Such nanoscale thermal‐confined generator can programmatically fine‐tune expression recruit disseminated tumor (DTCs) through CXCL12‐CXCR4 axis while avoiding cytokine storm, subsequently release DTC‐derived trigger immunity. Notably, B‐cell cluster, expressing regulatory signaling molecules Ptpn6 , Ms4a1 Cd52 identified playing key role single‐cell RNA sequencing. Moreover, such availably assuages effusion PM orthotopic gastric metastatic model. Overall, this work offers perspective on provides configurable strategy activating anti‐DTC

Language: Английский

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Reprogramming peritoneal macrophages with outer membrane vesicle-coated PLGA nanoparticles for endometriosis prevention

Biomaterials, Journal Year: 2025, Volume and Issue: 319, P. 123198 - 123198

Published: Feb. 17, 2025

Language: Английский

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The phenogenomic landscapes of pleural mesothelioma tumor microenvironment predict clinical outcomes

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 20, 2025

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with limited therapeutic options. To improve patients management treatment, more precise stratification strategies are needed. This study aimed to characterize the phenogenomic landscapes of MPM understand their influence on clinical outcomes. We conducted analysis 22 using two high throughput approaches: imaging mass cytometry (IMC) whole exome sequencing (WES). Resulting profiles were addressed for relevance predict prognosis. IMC revealed highly heterogeneous tumor microenvironment (TME) distinct cell subpopulations. Notably, we identified novel sarcomatoid-like cellular cluster associated poor The TME was also infiltrated immune cells including macrophages CD4+ T lymphocytes, that abundant in favorable WES complex genomic landscape prognostic value individual genetic alterations. However, mutational burden (TMB) emerged as potential predictive biomarker, inversely correlating infiltration, particularly lymphocytes. Our findings underscore intricate interplay between genome, composition, outcomes MPM. These data support integrating profiling develop patient potentially optimize approaches, immunotherapy.

Language: Английский

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M2-like tumor-associated macrophages may promote tumor progression in malignant pleural mesothelioma

Translational Oncology, Journal Year: 2025, Volume and Issue: 54, P. 102324 - 102324

Published: Feb. 20, 2025

Language: Английский

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Mesothelioma cell heterogeneity identified by single cell RNA sequencing

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 13, 2025

Mesothelioma cell heterogeneity encompasses diverse morphological and molecular characteristics observed within tumors, significantly impacting disease progression, treatment outcomes, the development of targeted therapies. This has long posed challenges for accurate diagnosis effective treatment, but understanding its complexities offers potential novel diagnostic modalities therapeutic interventions. study employed single-cell RNA sequencing (scRNA-seq) to investigate mesothelioma from various sources, including culture (CC), peritoneal lavage (Lav) tumor microenvironment, circulating cells (CTC) in murine models. Gene set enrichment analysis was used identify distinct gene signatures each subpopulation. The results revealed unique depending on their origin. In CC group, up-regulated genes were primarily involved cycle control, proliferation, apoptosis. CTC associated with cancer stemness. Lav group showed facilitating interactions between such as epithelial–mesenchymal transition immune responses mediated by IFN-α IFN-γ. Some pathways shared among all cells, suggesting transitioning functional states under specific conditions. may be first explore using scRNA-seq. identified subpopulation likely play critical roles initiation offering targets intervention. These findings could help inform more effective, personalized treatments mesothelioma, ultimately improving patient outcomes.

Language: Английский

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Malignant mesothelioma-associated inflammatory microenvironment promotes tumor progression via GPNMB

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 18, 2025

Tumor-Associated Macrophages (TAMs) are the main immune component of tumor stroma with heterogeneous functional activities, predominantly suppressing response and promoting progression, also via secretion different factors. Among these, GPNMB (Glycoprotein non-metastatic B) is usually associated disease progression in several types. Malignant pleural mesothelioma (MPM) a severe neoplasia poor prognosis, characterized by an abundancy TAMs, testifying presence long-lasting inflammation which pathogenetic disease. However, role MPM unclear. Clinical samples from patients were used to measure RNA protein levels GPNMB. The vivo was studied orthotopic mouse model using murine cell lines AB1 AB22. Experiments included growth wild type GPNMB-deficient mice blocking GPNMB-induced signaling anti-CD44 antibodies. We show that human tissues mainly produced infiltrating TAMs. Gpnmb TCGA significantly lower survival. Using we observed GPNMB-defective (DBA2/J mice) unable produce protein, tumors formed AB22 cells grow less than GPNMB-proficient (DBA2/J-Gpnmb+ mice), indicating host involved progression. Likewise, ectopic expression causes acceleration vivo, compared mock-transduced cells. Treatment tumor-bearing (a major receptor for GPNMB) results significant reduction growth. Overall, these indicate GPNMB, product marker gene driver may constitute promising therapeutic target.

Language: Английский

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DNA methylation-regulated HLA-C expression modulates immune responses and metabolic alterations to influence prognosis in mesothelioma

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(5)

Published: March 25, 2025

Malignant mesothelioma is a highly aggressive cancer with poor prognosis and limited therapeutic options. The tumor microenvironment (TME) plays pivotal role in driving progression, immune cells influencing disease outcomes. However, the molecular mechanisms underpinning mesothelioma's progression remain insufficiently understood. HLA-C, class I major histocompatibility complex (MHC) molecule, has been implicated modulation but its specific yet to be thoroughly investigated. This study employed comprehensive multi-omics approach, integrating single-cell RNA sequencing, expression quantitative trait loci (eQTL) analysis, Mendelian randomization (MR), elucidate of HLA-C progression. We first analyzed within TME, particular focus on cells, especially macrophages. Survival analysis was conducted using data from TCGA cohort assess clinical relevance expression. utilized mediated MR investigate impact DNA methylation expression, identifying key mediators such as inflammatory cytokines, cell populations, blood types, metabolites that could potentially influence patient prognosis. predominantly expressed macrophages, T NK higher levels were associated improved survival. revealed regulates which turn impacts Mediated encompassing 91 731 1400 metabolites, highlighted several critical HLA-C's effect prognosis, including IL-10, CD33 CD33dim HLA DR- myeloid reticulocyte perturbation response, ADP-to-citrate ratio. Gene set enrichment (GSEA) showed significant immune-related pathways patients high regulated by methylation, central modulating responses, metabolic processes TME. Our findings suggest serve both prognostic biomarker potential target for mesothelioma, offering new insights into this cancer.

Language: Английский

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Interplay between oncolytic measles virus, macrophages and cancer cells induces a proinflammatory tumor microenvironment

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

Published: July 10, 2024

Attenuated measles virus (MV) exerts its oncolytic activity in malignant pleural mesothelioma (MPM) cells that lack type-I interferon (IFN-I) production or responsiveness. However, other the tumor microenvironment (TME), such as myeloid cells, possess functional antiviral pathways. In this study, we aimed to characterize interplay between MV and human MPM. We cocultured MPM cell lines with monocytes macrophages infected them MV. analyzed transcriptome of each type studied their secretion phenotypes by high-dimensional flow cytometry. also measured transgene expression using an encoding GFP (MV-GFP). show drive differentiation into M2-like macrophages. These inhibit harboring a defect IFN-I signaling downstream receptor, while having minimal effects on responsiveness IFN-I. Interestingly, inhibition ruxolitinib restores cells. Upon infection, express pro-inflammatory genes induce IFN-stimulated increases HLA costimulatory molecules phagocytic activity. Finally, induces inflammatory cytokines, especially IFN-I, PD-L1 results reduce viral proteins some through generate may stimulate patient's anti-tumor immune response.

Language: Английский

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