Reprogramming the immunosuppressive tumor microenvironment through nanomedicine: an immunometabolism perspective

EBioMedicine, Год журнала: 2024, Номер 107, С. 105301 - 105301

Опубликована: Авг. 23, 2024

Increasing evidence indicates that immunotherapy is hindered by a hostile tumor microenvironment (TME) featured with deprivation of critical nutrients and pooling immunosuppressive metabolites. Tumor cells outcompete immune effector for essential nutrients. Meanwhile, wide range cell-derived toxic metabolites exerts negative impacts on anti-tumor response, diminishing the efficacy immunotherapy. Nanomedicine excellent targetability offers novel approach to improving cancer via metabolically reprogramming TME. Herein, we review recent strategies enhancing immunotherapeutic effects through rewiring metabolism nanomedicine. Attention drawn immunometabolic tactics stromal in TME Additionally, discuss future directions developing metabolism-regulating nanomedicine precise efficacious

Язык: Английский

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Metabolic regulation of the immune system in health and diseases: mechanisms and interventions

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 9, 2024

Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes functions of immune cells. The regulation system is important in pathogenesis progression numerous diseases, such as cancers, autoimmune diseases diseases. concept immunometabolism was introduced over a decade ago to elucidate intricate interplay between metabolism immunity. definition has expanded from chronic low-grade inflammation reprogramming cells various With being proposed developed, can be gradually summarized becomes more clearer. In context many cancer, disease, occurs inducing proinflammatory or anti-inflammatory effects. phenotypic functional changes caused by further affect development Based on experimental results, targeting cellular promising therapy. this review, we focus introduce their pathways reprogramming, summarize how these effects We thoroughly explore targets treatments based existing studies. challenges translating results into clinical applications field are also summarized. believe that better understanding health will improve management most

Язык: Английский

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Inhibition of glycolysis-driven immunosuppression with a nano-assembly enhances response to immune checkpoint blockade therapy in triple negative breast cancer

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 2, 2023

Abstract Immune-checkpoint inhibitors (ICI) are promising modalities for treating triple negative breast cancer (TNBC). However, hyperglycolysis, a hallmark of TNBC cells, may drive tumor-intrinsic PD-L1 glycosylation and boost regulatory T cell function to impair ICI efficacy. Herein, we report tumor microenvironment-activatable nanoassembly based on self-assembled aptamer-polymer conjugates the targeted delivery glucose transporter 1 inhibitor BAY-876 (DNA-PAE@BAY-876), which remodels immunosuppressive TME enhance response. Poly β-amino ester (PAE)-modified CTLA-4-antagonizing aptamers (aptPD-L1 aptCTLA-4) synthesized co-assembled into supramolecular nanoassemblies carrying BAY-876. The acidic microenvironment causes PAE protonation triggers dissociation initiate aptamer release. selectively inhibits glycolysis deprive uridine diphosphate N-acetylglucosamine downregulate N-linked glycosylation, thus facilitating recognition aptPD-L1 anti-PD-L1 therapy. Meanwhile, treatment also elevates supply tumor-residing cells (Tregs) metabolically rewiring them an immunostimulatory state, cooperating with aptCTLA-4-mediated immune-checkpoint inhibition abolish Treg-mediated immunosuppression. DNA-PAE@BAY-876 effectively reprograms in preclinical models female mice provides distinct approach immunotherapy clinics.

Язык: Английский

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Metabolic adaptations in prostate cancer

British Journal of Cancer, Год журнала: 2024, Номер 131(8), С. 1250 - 1262

Опубликована: Июль 5, 2024

Prostate cancer is one of the most commonly diagnosed cancers in men and a major cause cancer-related deaths worldwide. Among molecular processes that contribute to this disease, weight metabolism has been placed under limelight recent years. Tumours exhibit metabolic adaptations comply with their biosynthetic needs. However, metabolites also play an important role supporting cell survival challenging environments or remodelling tumour microenvironment, thus being recognized as hallmark cancer. uniquely driven by androgen receptor signalling, knowledge influenced paths research. This review provides comprehensive perspective on support prostate progression beyond particular focus intrinsic extrinsic pathways.

Язык: Английский

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Tumor metabolic regulators: key drivers of metabolic reprogramming and the promising targets in cancer therapy

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Янв. 9, 2025

Metabolic reprogramming within the tumor microenvironment (TME) is a hallmark of cancer and crucial determinant progression. Research indicates that various metabolic regulators form network in TME interact with immune cells, coordinating response. dysregulation creates an immunosuppressive TME, impairing antitumor In this review, we discuss how affect cell crosstalk TME. We also summarize recent clinical trials involving challenges metabolism-based therapies translation. word, our review distills key regulatory factors their mechanisms action from complex metabolism, identified as regulators. These provide theoretical basis research direction for development new strategies targets therapy based on reprogramming. Refining Depicting between stromal cells during Emphasizing unresolved translation advantages personalized treatment. Providing support therapies.

Язык: Английский

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Engineered Tumor–Immune Microenvironment On A Chip to Study T Cell–Macrophage Interaction in Breast Cancer Progression

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(14)

Опубликована: Фев. 15, 2024

Evolving knowledge about the tumor-immune microenvironment (TIME) is driving innovation in designing novel therapies against hard-to-treat breast cancer. Targeting immune components of TIME has emerged as a promising approach for cancer therapy. While recent immunotherapies aim at restoring antitumor immunity, counteracting tumor escape remains challenging. Hence there pressing need to better understand complex crosstalk within TIME. Considering this imperative, study aims investigating between two abundant cell populations TIME-macrophages and T cells, progression using an organotypic 3D vitro tumor-on-a-chip (TOC) model. The TOC features distinct yet interconnected stromal entities. This triculture platform mimics TIME, embedding suitable matrix. Analysis invasion, morphometric measurements, flow cytometry results underscores substantial contribution macrophages progression, while presence cells associated with deceleration migratory behavior both macrophages. Furthermore, cytokine analyses reveal significant upregulation leptin RANTES (regulated on activation, normal Cell expressed secreted) triculture. Overall, highlights complexity critical role progression.

Язык: Английский

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Programmable melanoma-targeted radio-immunotherapy via fusogenic liposomes functionalized with multivariate-gated aptamer assemblies

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 12, 2024

Radio-immunotherapy exploits the immunostimulatory features of ionizing radiation (IR) to enhance antitumor effects and offers emerging opportunities for treating invasive tumor indications such as melanoma. However, insufficient dose deposition immunosuppressive microenvironment (TME) solid tumors limit its efficacy. Here we report a programmable sequential therapeutic strategy based on multifunctional fusogenic liposomes (Lip@AUR-ACP-aptPD-L1) overcome intrinsic radio-immunotherapeutic resistance tumors. Specifically, are loaded with gold-containing Auranofin (AUR) inserted multivariate-gated aptamer assemblies (ACP) PD-L1 aptamers in lipid membrane, potentiating melanoma-targeted AUR delivery while transferring ACP onto cell surface through selective membrane fusion. amplifies IR-induced immunogenic death melanoma cells release antigens damage-associated molecular patterns adenosine triphosphate (ATP) triggering adaptive immunity. AUR-sensitized radiotherapy also upregulates matrix metalloproteinase-2 (MMP-2) expression that combined released ATP activate an "and" logic operation-like process (AND-gate), thus in-situ engineered cytosine-phosphate-guanine aptamer-based immunoadjuvants (eCpG) stimulating dendritic cell-mediated T priming. Furthermore, inhibits tumor-intrinsic vascular endothelial growth factor signaling suppress infiltration fostering anti-tumorigenic TME. This study approach treatment clinics.

Язык: Английский

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Targeting purine metabolism-related enzymes for therapeutic intervention: A review from molecular mechanism to therapeutic breakthrough

International Journal of Biological Macromolecules, Год журнала: 2024, Номер unknown, С. 136828 - 136828

Опубликована: Окт. 1, 2024

Язык: Английский

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Photoredox-Mediated Immunotherapy Utilizing Rhenium(I) Photocatalysts with Electron Donor–Acceptor–Donor Configuration

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

The hypoxic environment of solid tumors significantly diminishes the therapeutic efficacy oxygen-dependent photodynamic therapy. Developing efficient photosensitizers that operate via photoredox catalysis presents a promising strategy to overcome this challenge. Herein, we report rational design two rhenium(I) tricarbonyl complexes (Re-TPO and Re-TP) with electron donor–acceptor–donor configuration. Notably, Re-TP exhibits aggregation-induced emission properties enhanced spin–orbit coupling compared Re-TPO, thus exhibiting promoted photosensitizing capability. In addition generating type I II reactive oxygen species, excited facilitates photocatalytic oxidation NADH NAD+ photoreduction pyruvic acid lactic acid. This metabolic intervention triggers PD-L1-linked immune responses disrupts tumor redox balance, leading ferroptosis immunogenic cell death. combined immunotherapy effects suppress both primary distant B16 tumors. investigation provides compelling model for designing metal-based PSs photoredox-mediated photoimmunotherapy against

Язык: Английский

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Lactylation modification in cancer: mechanisms, functions, and therapeutic strategies

Experimental Hematology and Oncology, Год журнала: 2025, Номер 14(1)

Опубликована: Март 8, 2025

Cancer remains the leading cause of mortality worldwide, and emergence drug resistance has made identification new therapeutic targets imperative. Lactate, traditionally viewed as a byproduct glycolysis with limited ATP-producing capacity, recently gained recognition critical signaling molecule. It plays key role not only in cancer cell metabolism but also shaping tumor microenvironment (TME). Histone lysine lactylation, newly identified post-translational modification, been shown to influence range cellular processes cancer. Current research focuses on mechanisms functions histone lactylation cancer, including its gene expression regulation, signal transduction, protein synthesis. However, despite these advancements, there are still plenty barriers quest unravel modification. The single-cell spatial transcriptomics may offer valuable insights for selecting targets. This review provides comprehensive summary applications modification clinical settings. Through detailed analysis, we identify challenges limitations that exist current landscape. These lay groundwork future studies by highlighting promising directions.

Язык: Английский

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