Tumor‐Associated Macrophages Nano‐Reprogrammers Induce “Gear Effect” to Empower Glioblastoma Immunotherapy

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

Published: Jan. 10, 2025

Abstract Glioblastoma (GBM), the most malignant brain tumor with high prevalence, remains highly resistant to existing immunotherapies due significant immunosuppression within microenvironment (TME), predominantly manipulated by M2‐phenotypic tumor‐associated macrophages (M2‐TAMs). Here in this work, an M2‐TAMs targeted nano‐reprogrammers, MG5‐S‐IMDQ, is established decorating mannose molecule as targeting moiety well toll‐like receptor (TLR) 7/8 agonist, imidazoquinoline (IMDQ) on dendrimeric nanoscaffold. MG5‐S‐IMDQ demonstrated excellent capacity of penetrating blood‐brain barrier (BBB) selectively GBM microenvironment, leading a phenotype transformation and function restoration TAMs shown heightened phagocytic activity toward cells, enhanced cytotoxic effects, improved antigen cross‐presentation capability. In meantime, induction function‐oriented “gear effect”, treatment extended its impact systemically enhancing infiltration type I conventional dendritic cells (cDC1s) into sites bolstering adaptive immune responses. sum, precisely working unique target situ, nano‐reprogrammers successfully robust network that worked synergistically combat tumors. This facile nanoplatform‐based immunomodulatory strategy, serving powerful convenient monotherapy or complementary alongside other therapies like surgery, provided deep insights for advancing translational study GBM.

Language: Английский

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ScRNA-seq unveils the functional characteristics of glioma-associated macrophages and the regulatory effects of chlorogenic acid on the immune microenvironment—a study based on mouse models and clinical practice

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

Glioma is the most common primary malignant brain tumor. Despite advances in surgical techniques and treatment regimens, therapeutic effects of glioma remain unsatisfactory. Immunotherapy has brought new hope to patients, but its outcomes are limited by immunosuppressive nature tumor microenvironment (TME). This study aimed reveal subpopulations functional characteristics tumor-associated macrophages (TAMs) explore regulatory chlorogenic acid (CHA) on immune microenvironment, as well potential for clinical application. In this study, CHA was used model mice. ScRNA - seq analysis conducted elucidate differentiation trajectories bone marrow derived monomacrophages (BMDMs) microglia. A PPI molecular docking were constructed using target prediction database. case a patient treated with reviewed. slowed growth mice extended survival time It enhanced antigen presenting function T cell activation related gene expression, activated microglia through JAK STAT pathway, improved antitumor functions. The good affinity STAT1 confirmed. survived 5 years 6 months, achieved partial remission (PR) after 9 months treatment, remained alive without any symptoms or toxic side effects. Our revealed subtypes TAMs. significantly modulating BMDMs may provide insights into targeting regulation TME offer theoretical practical support application CHA. results demonstrated improving effects, which could have implications future strategies.

Language: Английский

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A Neuroimmune‐Oncology Microphysiological Analysis Platform (NEO‐MAP) for Evaluating Astrocytic Scar Formation and Microgliosis in Glioblastoma Microenvironment

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

Published: March 12, 2025

Abstract Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, characterized by its heterogeneity in cellular components, including reactive astrocytes and microglia. Since neuroimmune responses like astrogliosis microgliosis gain recognition as vital factors tumor progression, there a growing need for clinically relevant models that assess interactions between astrocytes, microglia, GBM. Here, NEuroimmune‐Oncology Microphysiological Analysis Platform (NEO‐MAP) presented “new map” to observe astrocytic scar formation response NEO‐MAP based on pathophysiological principles designed replicate GBM‐glia interactions, multi‐phenotypic microglia activities, scar‐forming with chondroitin sulfate proteoglycans (CSPGs) extracellular matrix, biophysical characteristics barrier. The reveals inhibiting mTORC2 GBM promotes proinflammatory transformation enhanced formation. Astrocytes form scars prompted change from M2 M1 phenotype, enhancing chemotherapy sensitivity. Tissues patients show significant correlation reduced activity increased astrogliosis, alongside decrease M2‐polarized microgliosis, aligning findings. Overall, foreseen tool exploring tumor‐glia opening avenues drug development aimed at microenvironment.

Language: Английский

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Tumor-associated macrophages correlate with better outcome in SHH medulloblastoma

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 15, 2025

Objective Tumor-associated macrophages (TAMs) constitute a significant proportion of the immune cell population within brain tumors. The polarization exerts an important influence on tumor microenvironment (TME). Nevertheless, specific role TAMs in sonic hedgehog (SHH) medulloblastoma remains unclear. To investigate characteristics and effects SHH medulloblastoma, we evaluated infiltration M1 M2 tissues analyzed correlation between recruitment clinical outcome patients. Methods We enrolled total 42 patients diagnosed with medulloblastoma. Using multiple immunofluorescence staining paraffin-embedded sections, detected activated phenotype (M1/M2) by monoclonal antibodies for CD68, HLA-DR CD163. Subsequently, as well prognostic factors. Results median age (31 boys, 11 girls) was 5.3 years (range: 0.8-15.1 years). All had confirmed pathological types, including 4 cases classic (CMB), 33 desmoplastic/nodular (DNMB), 3 extensive nodularity (MBEN), 2 large-cell/anaplastic (LCA). Thirteen presented metastasis at diagnosis, while twenty-nine were without metastasis. Four high-risk genetic abnormalities. Different proportions found collected tissues, large amounts CD68 + CD163 cells found. study revealed that M (total macrophages) mix (CD68 cells) significantly higher group <5 old ( P < 0.05), non-metastatic than metastatic = 0.043). CMB DNMB/MBEN 0.036), children abnormalities 0.007). Five-year PFS poorer ≥5 0.05). High better 5-year 0.000), whereas high both OS 0.001, 0.001). Multivariate analysis showed independent factors PFS, factor OS. Conclusion increase predicts especially might be therapeutic target

Language: Английский

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Therapeutic potential of arginine deprivation therapy for gliomas: a systematic review of the existing literature

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 22, 2024

Background Arginine deprivation therapy (ADT) hinders glioma cells’ access to nutrients by reducing peripheral blood arginine, showing great efficacy in various studies, which suggests it as a potentially promising treatment for glioma. The aim of this systematic review was explore the mechanism ADT gliomas, therapeutic effect based on existing research, and possible combination therapies. Methods We performed literature PubMed, ScienceDirect Web Science databases according PRISMA guidelines, searching articles Results identified 17 studies among 786 search results, mainly free condition, Deiminase Arginase, including three completed clinical trials. has shown results vivo vitro , with its safety confirmed In early phase treatment, glioblastoma (GBM) cells develop protective mechanisms stress autophagy, eventually evolve into caspase dependent apoptosis or senescence, respectively. immunosuppressive microenvironment is also altered arginine depletion, such transformation microglia pro-inflammatory phenotype activation T-cells. Thus, demonstrates glioma-killing presence mechanisms. conventional therapies investigational drugs radiotherapy, temozolomide (TMZ), cyclin-dependent kinase inhibitors (CDK) autophagy inducers, been be more effective. However, phenomenon drug resistance due re-expression ASS1 rather than stem cell remains investigated. Conclusion Despite paucity literature, available data demonstrate potential encourage further especially exploration extrapolation what we know about effects from other tumors

Language: Английский

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β-Mangostin targets and suppresses glioma via STING activation and tumor-associated microglia polarization

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117074 - 117074

Published: July 6, 2024

Glioma, a common and highly malignant central nervous system tumor, markedly influences patient prognosis via interactions with glioma-associated macrophages. Previous research has revealed the anticancer potential of β-mangostin, xanthone derivative obtained from mangosteen fruit. This investigated role β-mangostin on microglia in glioma microenvironment evaluated efficacy combined anti-PD-1 antibody (αPD-1) glioma-bearing mice. The results showed that, attenuated M2 polarization BV2 cells promoted M1-related interleukin (IL)-1β IL-6 secretion, thereby inhibiting invasion. In addition, improved anti-glioma effects αPD-1 increased CD8

Language: Английский

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ScRNA-seq Unveils the Functional Characteristics of Glioma-Associated Macrophages and the Regulatory Effects of Chlorogenic Acid on the Immune Microenvironment—A Study Based on Mouse Models and Clinical Practice

Published: Aug. 6, 2024

Glioma is the most common primary malignant brain tumors. Despite advances in surgical techniques and treatment regimens, therapeutic effects remain unsatisfactory. Immunotherapy has brought new hope to glioma patients, but immunosuppressive nature of tumor microenvironment (TME) limited outcomes. This study aims reveal subpopulations functional characteristics tumor-associated macrophages (TAMs), explore regulatory chlorogenic acid on immune microenvironment, investigate its potential for clinical application. In this study, Chlorogenic slowed growth mouse model extended survival time mice. ScRNA-seq analysis elucidated differentiation trajectories BMDMs microglia, revealing these two populations. It enhanced antigen-presenting function gene expression related T-cell activation, activated microglia through JAK-STAT pathway, improved antitumor functions. Using target prediction database, a PPI molecular docking were constructed, confirming good affinity with STAT1. A case patient treated was reviewed, who survived 5 years 6 months, achieved partial remission (PR) after 9 months treatment, remains alive no symptoms or toxic side effects. Our revealed subtypes macrophages. significantly by modulating bone marrow-derived mono-macrophages (BMDMs) demonstrating provides insights targeting regulation TME offers theoretical practical support application acid.

Language: Английский

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Glioblastoma-associated macrophages: A key target in overcoming Glioblastoma therapeutic resistance

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Revolutionizing Neuroimmunology: Unraveling Immune Dynamics and Therapeutic Innovations in CNS Disorders

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13614 - 13614

Published: Dec. 19, 2024

Neuroimmunology is reshaping the understanding of central nervous system (CNS), revealing it as an active immune organ rather than isolated structure. This review delves into unprecedented discoveries transforming field, including emerging roles microglia, astrocytes, and blood–brain barrier (BBB) in orchestrating neuroimmune dynamics. Highlighting their dual both repair disease progression, we uncover how these elements contribute to intricate pathophysiology neurodegenerative diseases, cerebrovascular conditions, CNS tumors. Novel insights microglial priming, astrocytic cytokine networks, meningeal lymphatics challenge conventional paradigms privilege, offering fresh perspectives on mechanisms. work introduces groundbreaking therapeutic innovations, from precision immunotherapies controlled modulation BBB using nanotechnology focused ultrasound. Moreover, explore fusion with neuromodulatory technologies, underscoring new frontiers for personalized medicine previously intractable diseases. By synthesizing advancements, propose a transformative framework that integrates cutting-edge research clinical translation, charting bold path toward redefining management era neuroimmunology.

Language: Английский

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