Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota

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

Published: Feb. 7, 2025

Despite the approval of several artificial nanotherapeutics for treatment triple-negative breast cancer (TNBC), significant challenges, including unsatisfactory therapeutic outcomes, severe side effects, and high cost large-scale production, still restrict their long-term application. In contrast, plant-derived extracellular vesicles (PEVs) exhibit promising potential in therapy due to negligible systemic toxicity, bioavailability cost- effectiveness. this study, we developed an alternative strategy inhibit TNBC via Platycodon grandiflorum (PG)-derived (PGEVs). The PGEVs were isolated by ultracentrifugation sucrose gradient centrifugation method contained adequate functional components such as proteins, lipids, RNAs active molecules. exhibited remarkable stability, tolerating acidic digestion undergoing minimal changes simulated gastrointestinal fluid. They efficiently taken up tumor cells induced increased production reactive oxygen species (ROS), leading cell proliferation inhibition apoptosis, particularly line 4T1. Additionally, facilitated polarization tumor-associated macrophages (TAMs) toward M1 phenotype secretion pro-inflammatory cytokines. Further vivo investigations revealed that accumulated 4T1 tumors exerted effects through boosting anti-tumor immune responses modulating gut microbiota whether administered orally or intravenously (i.v.). conclusion, these findings highlight a natural, biocompatible efficient nanotherapeutic candidate treating TNBC.

Language: Английский

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Prognostic value of CD163+ macrophages in solid tumor malignancies: A scoping review

Immunology Letters, Journal Year: 2025, Volume and Issue: unknown, P. 106970 - 106970

Published: Jan. 1, 2025

Tumor-associated macrophages (TAMs) play crucial roles in development and progression of malignant diseases. Notably, CD163

Language: Английский

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Anti-Inflammatory Effects of SGLT2 Inhibitors: Focus on Macrophages

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1670 - 1670

Published: Feb. 15, 2025

A growing body of evidence indicates that nonglycemic effects sodium-glucose cotransporter 2 (SGLT2) inhibitors play an important role in the protective these drugs diabetes, chronic kidney disease, and heart failure. In recent years, anti-inflammatory potential SGLT2 has been actively studied. This review summarizes results clinical experimental studies on activity inhibitors, with a special focus their macrophages, key drivers metabolic inflammation. patients type therapy reduces levels inflammatory mediators. diabetic non-diabetic animal models, control low-grade inflammation by suppressing activation tissue recruitment monocytes from bloodstream, macrophage polarization towards M1 phenotype. The molecular mechanisms macrophages include attenuation inflammasome inhibition TLR4/NF-κB pathway, as well modulation other signaling pathways (AMPK, PI3K/Akt, ERK 1/2-MAPK, JAKs/STAT). discusses state-of-the-art concepts prospects further investigations are needed to obtain deeper insight into underlying molecular, cellular, physiological levels.

Language: Английский

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Immunometabolism of tumor-associated macrophages: a therapeutic perspective

European Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 115332 - 115332

Published: Feb. 1, 2025

Language: Английский

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SPP1 macrophages across diseases: A call for reclassification?

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(5)

Published: March 6, 2025

SPP1+ macrophages, characterized by elevated expression of the osteopontin gene (secreted phosphoprotein 1, SPP1), have emerged as key players in various pathological contexts, including aging, chronic inflammatory diseases, and cancer. While frequently classified a subclass tumor-associated macrophages oncological settings, their presence noncancer conditions, such aging-related disorders muscular suggests broader role beyond tumors. These share conserved traits, fibrosis promotion, extracellular matrix remodeling, immune modulation, often linked to poor clinical outcomes. This perspective explores multifaceted roles across diseases advocates for reclassification distinct macrophage subtype associated with or prolonged inflammation. Recognizing cross-disease relevance could reshape biology inform targeted therapeutic strategies.

Language: Английский

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Exploring the Prognostic Role of Trop-2, CD47, and CD163 Expression Levels on Survival Outcomes in Patients with Triple-Negative Breast Cancer

Diagnostics, Journal Year: 2025, Volume and Issue: 15(2), P. 232 - 232

Published: Jan. 20, 2025

Background: This study evaluated the prognostic impact of Trop-2, CD47, and CD163 expression on clinical outcomes in triple-negative breast cancer (TNBC) investigated their interactions with tumor progression. Methods: A retrospective cohort 92 patients TNBC was analyzed. The scores for were categorized as negative/low (0–3 points) or high (4–6 points). primary endpoint overall survival (OS). Results: median age 50 years old. High Trop-2 observed 55.4% significantly associated advanced disease stage (p < 0.001). CD47 (44.6%) correlated = 0.044), whereas (45.7%) 0.021), absence comorbidities 0.022), lower pT 0.023). Moderate positive correlations found between 0.037), 0.001), respectively. Kaplan–Meier analysis revealed that low exhibited prolonged OS 0.021) progression-free (PFS) 0.026) compared to those expression. Univariate multivariate analyses significant associations PFS lymphovascular invasion, BRCA status. Conclusions: is a factor worse outcomes. Although showed trends poorer prognosis, significance not confirmed. These findings offer promising prospects future studies combined antibody–drug conjugates (ADCs), they may present opportunities address multiple resistance mechanisms management enhance

Language: Английский

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Zn-doped CaP coating equips Ti implants with corrosion resistance, biomineralization, antibacterial and immunotolerant activities

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Formononetin Affects Polarization of M2 Macrophages Through the Jak2/Stat3 Pathway in Hcc

Published: Jan. 1, 2025

Language: Английский

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Engineered oncolytic virus coated with anti-PD-1 and alendronate for ameliorating intratumoral T cell hypofunction

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: Feb. 15, 2025

Abstract Background Glioblastoma is a highly aggressive and devastating primary brain tumor that resistant to conventional therapies. Oncolytic viruses represent promising therapeutic approach for glioblastoma by selectively lysing cells eliciting an anti-tumor immune response. However, the clinical efficacy of oncolytic often hindered challenges such as short persistence, host antiviral responses, T cell dysfunction. Methods We have developed novel strategy “dressing” with anti-PD-1 antibodies alendronate (PD-1/Al@OV) prevent premature clearance enhance function, thereby improving immunotherapy outcomes against glioma. Results found in high reactive oxygen species environment tumor, PD-1/Al@OV disassembled release viruses, anti-PD-1, alendronate. The released blocked PD-1/PD-L1 pathway, activating cells; eliminated tumor-associated macrophages, increasing concentration viruses; directly lysed cancer cells, enhancing intratumoral infiltration. Conclusion This effectively improved immunosuppressive microenvironment achieved robust effect. Consequently, this study presents combination therapy improvement microenvironment, offering new prospects application viruses.

Language: Английский

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Oropharyngeal carcinomas induce circulating monocytes to express a TAM-like pro-tumor expression profile that suppresses T-cell proliferation

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 19, 2025

Introduction Tumor-associated macrophages (TAMs) recruited from circulating monocytes drive tumor-growth and establish an immunosuppressive tumor microenvironment (TME). Initial events in transition resting to TAMs are poorly understood. Here, we report that oropharyngeal cancer (OPC) patients control treated with OPC-conditioned media (CM) express a repertoire of pro-tumor mediators is characteristic TAMs. Methods Monocytes were stimulated OPC cell line CM, analyzed by single-cell RNAseq. Results select genes confirmed qPCR tumors vs. clinically normal tissue. spheroids containing T-cells established, TAM phenotype characterized flow analysis qPCR, T-cell proliferation assessed flow. induced multiple including CXCL1, CXCL5, CXCL8, SPP1, IL1B, GPNMB , FABP5 . Patient had higher baseline levels or achieved after stimulation than monocytes. A subset patient high CXCL9/-10/-11 expression resisted downregulation response stimulation, potential sign more favorable TME. biopsies compared tissue correlated outcome. Spheroid derived maintained the seen conditioned media. These suppress proliferation. Inhibition COX-2 IL1 signaling during differentiation into partially blocked suppression Conclusion Targeting early could be used develop new therapies for OPC.

Language: Английский

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