Enhancing anti-tumor immunity through liposomal oxaliplatin and localized immunotherapy via STING activation

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 357, P. 531 - 544

Published: April 21, 2023

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a promising approach for anti-cancer immunotherapy by bridging innate and adaptive immunity. Recent evidence suggests that chemotherapy-induced DNA damage can directly induce dendritic cell (DC) maturation recruitment, which synergizes with STING activation to enhance anti-tumor effects. As an immunogenic death (ICD) inducer, oxaliplatin generates massive double-stranded (dsDNA) crosslinks, release tumor-associated antigens promoting the "eat me" signal. improves antigen immunogenicity, promote T infiltration. In this study, we developed liposomes encapsulating combine formulation agonist (ADU-S100) treating colorectal cancer. efficiently inhibited proliferation tumor cells while induced ICD in CT26 cancer cells, enhanced phagocytosis vitro. liposome-based immunochemotherapy exhibited strongest efficacy, resulting complete remission upon inoculation. Mechanistic studies showed potent effect was related significant recruitment infiltrating CD8 CD4 reduction suppressive Treg shift phenotype macrophages immune stimulating macrophages. Thus, our study demonstrated potential combining oxaliplatin-loaded reduce growth regulating immunosuppressive state tumor.

Language: Английский

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Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 3033 - 3033

Published: Feb. 3, 2023

Immunogenic cell death (ICD) is a form of programmed with strong sense inflammatory detection, whose powerful situational awareness can cause the reactivation aberrant immunity. However, role ICD in pathogenesis severe acute pancreatitis (SAP) has yet to be investigated. This study aims explore pivotal genes associated SAP and how they relate immune infiltration short-chain fatty acids (SCFAs), order provide theoretical foundation for further, in-depth mechanistic studies. We downloaded GSE194331 datasets from Gene Expression Omnibus (GEO). The use differentially expressed gene (DEG) analysis; weighted co-expression network analysis (WGCNA) least absolute shrinkage selection operator (LASSO) regression allowed us identify total three ICD-related hub (LY96, BCL2, IFNGR1) SAP. Furthermore, single sample set enrichment (ssGSEA) demonstrated that are closely specific cells, activation pathways metabolism SCFAs (especially butyrate). These findings were validated through expression patterns both clinical patients rat animal models In conclusion, first concept was proposed our study. important implications future investigations into pro-inflammatory mechanisms mediated by damage-associated molecular (DAMPs) late stages

Language: Английский

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Idebenone attenuates ferroptosis by inhibiting excessive autophagy via the ROS-AMPK-mTOR pathway to preserve cardiac function after myocardial infarction

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 943, P. 175569 - 175569

Published: Feb. 3, 2023

Cardiovascular diseases (CVDs) are the leading causes of mortality worldwide. As a type CVDs, myocardial infarction (MI) induces ischemia hypoxia, which leads to excessive reactive oxygen species (ROS), resulting in multiple cell deaths and contributing subsequent development heart failure or premature death. Recent evidence indicates that ROS-induced lipid peroxidation promotes autophagy ferroptosis, loss healthy myocardium dysfunction cardiac tissue. Theoretically, function would be preserved after MI by inhibiting ferroptosis. an analog coenzyme Q10 (CoQ10) clinically approved drug, idebenone used inhibit ferroptosis preserve due its capacity improve mitochondrial physiology with antioxidant anti-inflammatory properties. Here, we confirmed addition inhibited H2O2-induced RSL3-induced Furthermore, ROS-AMPK-mTOR pathway axis was identified as signaling stimulated prevent consequent In animal model, demonstrated cardioprotective role regulating ROS-dependent paves way for future clinical translation management.

Language: Английский

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Lipid‐based nanoparticles as drug delivery systems for cancer immunotherapy

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: Aug. 1, 2023

Abstract Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, patients without sufficient antitumor immunity, numerous data indicate that blocking the negative signals elicited by immune checkpoints is ineffective. Drugs stimulate activation‐related pathways are emerging as another route for improving immunotherapy. In addition, development of nanotechnology presents a promising platform tissue and cell type‐specific delivery improved uptake immunomodulatory agents, ultimately leading to enhanced immunotherapy reduced side effects. this review, we summarize discuss latest developments nanoparticles (NPs) immuno‐oncology therapy with focus on lipid‐based NPs (lipid‐NPs), including characteristics advantages various types. Using agonists targeting stimulation interferon genes (STING) transmembrane protein an exemplar, review potential lipid‐NPs augment STING agonist therapy. Furthermore, present recent findings underlying mechanisms how pathway activation fosters immunity regulates tumor microenvironment provide summary distinct preclinical studies clinical trials. Ultimately, conduct critical assessment obstacles future directions utilization enhance

Language: Английский

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Mechanisms of alkaliptosis

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Aug. 4, 2023

Malignant tumors represent a major threat to global health and the search for effective treatments is imperative. While various exist, including surgery, radiotherapy, chemotherapy, immunotherapy combination therapies, there remains need develop therapies that target regulated cell death pathways eliminate cancer cells while preserving normal cells. Alkaliptosis, pH-dependent process triggered by small molecular compound JTC801, has been identified as novel approach malignant tumor treatment, particularly in pancreatic cancer. Two signaling pathways, NF-κB-CA9 pathway ATP6V0D1-STAT3 pathway, contribute induction of alkaliptosis. This review summarizes recent developments our understanding alkaliptosis signals, mechanisms, modulation, explores its context-dependent effects on drug resistance, inflammation, immunity. By providing deeper heterogeneity plasticity this information holds promise informing design more anti-tumor therapies.

Language: Английский

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