International Journal of Biological Macromolecules, Год журнала: 2025, Номер 306, С. 141586 - 141586
Опубликована: Фев. 27, 2025
Язык: Английский
Frontiers in Pediatrics, Год журнала: 2024, Номер 12
Опубликована: Март 8, 2024
Pediatric high-grade glioma (pHGG) including pediatric glioblastoma (pGBM) are highly aggressive central nervous system (CNS) malignancies. pGBM comprises approximately 3% of all CNS malignancies and has a 5-year survival rate 20%. Surgical resection chemoradiation often the standard care for pHGG, however, even with these interventions, children diagnosed pHGG remains poor. Due to shortcomings associated care, many efforts have been made create novel immunotherapeutic approaches targeted These include use vaccines, cell-based therapies, immune-checkpoint inhibitors. However, it is believed that in patients an immunosuppressive tumor microenvironment (TME) possess barriers limit efficacy immune-based therapies. One includes presence myeloid cells. In this review we will discuss various types cells present TME, macrophages microglia, myeloid-derived suppressor cells, dendritic as well specific mechanisms can employ enable immunosuppression. Finally, highlight therapeutic strategies aimed at impeding myeloid-cell derived
Язык: Английский
Процитировано
9
Cell Reports Medicine, Год журнала: 2023, Номер 4(9), С. 101177 - 101177
Опубликована: Авг. 30, 2023
The role of brain immune compartments in glioma evolution remains elusive. We profile cells microenvironment and the matched peripheral blood from 11 patients. Glioblastoma exhibits specific infiltration blood-originated monocytes expressing epidermal growth factor receptor (EGFR) ligands EREG AREG, coined as tumor-associated (TAMo). TAMo is mutually exclusive with EGFR alterations (p = 0.019), while co-occurring mesenchymal subtype 4.7 × 10−7) marking worse prognosis 0.004 0.032 two cohorts). Evolutionary analysis initial-recurrent pairs single-cell study a multi-centric glioblastoma reveal association between elevated transformation. Further analyses identify FOSL2 master regulator demonstrates that FOSL2-EREG/AREG-EGFR signaling axis promotes invasion vitro. Collectively, we tumor its driving activating to shape evolution.
Язык: Английский
Процитировано
19
Cancer Immunology Research, Год журнала: 2024, Номер 12(3), С. 363 - 376
Опубликована: Янв. 30, 2024
Abstract Extensive infiltration by tumor-associated macrophages (TAM) in combination with myeloid-derived suppressor cells constitute the immunosuppressive microenvironment and promote malignant phenotype of gliomas. The aggressive mesenchymal (MES)-subtype glioma stem (GSC) are prominent However, underlying immune-suppressive mechanisms still unknown. current study showed that antitumor immune was activated Nfat1−/− mice, suggesting induction nuclear factor T cells-1 (NFAT1). In TAMs, NFAT1 could upregulate transcriptional activity complement 3 (C3) increase secretion C3a, which then bind to C3aR M2-like macrophage polarization activating TIM-3. Simultaneously, C3a/C3aR Ca2+-NFAT1 pathway, forming a positive feedback loop for further promoted MES transition GSCs. Finally, disruption this using inhibitor significantly inhibited growth both vitro vivo. demonstrated NFAT1-C3a-C3aR induces TAMs promotes GSCs, might be potential therapeutic target glioma.
Язык: Английский
Процитировано
8
Advanced Materials, Год журнала: 2024, Номер unknown
Опубликована: Авг. 29, 2024
Abstract Glioblastoma multiforme (GBM) remains incurable despite multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin (2–3 cm) of the initial resected lesion due to unreachable residual cancerous cells. Here, completely biodegradable microneedle for cavity delivery glioblastoma‐associated macrophages (GAMs)‐activating immune nano‐stimulator that mitigates glioblastoma is reported. The tumor lesion‐directed biocompatible releases and toll‐like receptor 9 agonist in controlled manner until microneedles degrade over 1 week, efferently induce situ phonotypic shifting GAMs from anti‐ pro‐inflammatory recurrence obviously inhibited. implantable offer significant improvement conventional transdermal ones, as they are 100% degradable, ensuring safe application cavities. It also revealed T cells recruited niche initiate anti‐tumor response eradicate Taken together, this work provides potential strategy immunomodulating postoperative mitigate patients, which may have broad applications other malignancies intervention.
Язык: Английский
Процитировано
8
Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)
Опубликована: Фев. 18, 2024
Abstract Background Overexpression of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is related to the exhaustion CD8 + tumor-infiltrating lymphocytes (TILs) in diffuse large B-cell lymphoma (DLBCL). However, mechanism TIM3-mediated TILs DLBCL remains poorly understood. Therefore, we aimed clarify potential pathway involved its significance DLBCL. Methods The expression TIM3 correlation with exhaustion, key ligand TIM3, were analyzed using single-cell RNA sequencing validated by sequencing. biological TIM3-related was investigated based on sequencing, immunohistochemistry, reverse transcription-quantitative polymerase chain reaction data. Finally, possible regulatory explored Results Our results demonstrated that TILs, especially terminally exhausted state, major clusters expressed Galectin-9, mainly M2 macrophages, can induce through TIM3/Galectin-9 pathway. Meanwhile, high enrichment immunosuppressive tumor microenvironment, severe clinical manifestations, inferior prognosis, poor response CHOP-based chemotherapy, predict efficacy immune checkpoint blockade therapy Furthermore, may be regulated IFN-γ signaling Conclusions study highlights plays a crucial role escape DLBCL, which facilitates further functional studies could provide theoretical basis for development novel immunotherapy
Язык: Английский
Процитировано
7
Pharmacological Research, Год журнала: 2024, Номер 209, С. 107458 - 107458
Опубликована: Окт. 11, 2024
Numerous preclinical studies have demonstrated the inhibitory function of T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) on cells as an receptor, leading to clinical development anti-Tim-3 blocking antibodies. However, recent shown that Tim-3 is expressed not only but also multiple types in tumor microenvironment (TME), including dendritic (DCs), natural killer (NK) cells, macrophages, and cells. Therefore, blockade immune affect influence functions other For example, can enhance ability DCs regulate innate adaptive immunity. The role NK controversial, it antitumor under certain conditions while having opposite effect situations. Additionally, promote reversal macrophage polarization from M2 phenotype M1 phenotype. Furthermore, inhibit by suppressing proliferation metastasis In summary, increasing evidence has plays a critical efficacy therapy. Understanding therapy non-T help elucidate diverse responses observed patients, better relevant therapeutic strategies. This review aims discuss TME emphasize impact beyond
Язык: Английский
Процитировано
6
Hepatology, Год журнала: 2023, Номер 79(2), С. 392 - 408
Опубликована: Июль 5, 2023
Background and Aims: The common characteristics of alcohol-associated liver injury (ALI) include abnormal function, infiltration inflammatory cells, generation oxidative stress. gastrin-releasing peptide receptor (GRPR) is activated by its neuropeptide ligand, (GRP). GRP/GRPR appears to induce the production cytokines in immune cells promotes neutrophil migration. However, effects ALI are unknown. Approach Results: We found high GRPR expression patients with steatohepatitis increased pro-GRP levels peripheral blood mononuclear these compared that control. Increased GRP may be associated histone H3 lysine 27 acetylation induced alcohol, which then binding. Grpr -/- flox/flox LysM Cre mice alleviated ethanol-induced relieved steatosis, lower serum alanine aminotransferase, aspartate triglycerides, malondialdehyde, superoxide dismutase levels, reduced influx, decreased release chemokines. Conversely, overexpression showed opposite effects. pro-inflammatory stress roles might dependent on IRF1-mediated Caspase-1 inflammasome NOX2-dependent reactive oxygen species pathway, respectively. In addition, we verified therapeutic preventive RH-1402, a novel antagonist, for ALI. Conclusions: A knockout or antagonist during excess alcohol intake could have anti-inflammatory antioxidative roles, as well provide platform modification-based therapy
Язык: Английский
Процитировано
13
iScience, Год журнала: 2024, Номер 27(3), С. 109270 - 109270
Опубликована: Фев. 22, 2024
Glioblastoma stem cells (GSCs) reside in hypoxic periarteriolar niches of glioblastoma micro-environment, however, the crosstalk GSCs with macrophages on regulating tumor angiogenesis and progression are not fully elucidated. GSCs-derived exosomes (GSCs-exos) essential mediators during immune-microenvironment remodeling initiated by GSCs, resulting M2 polarization tumor-associated (TAMs) as we reported previously. Our data disclosed aberrant upregulation miR-374b-3p both clinical specimens human cell lines GSCs. MiR-374b-3p level was high GSCs-exos can be internalized macrophages. Mechanistically, exosomal induced downregulating phosphatase tensin expression, thereby promoting migration tube formation vascular endothelial after coculture Cumulatively, these indicated that enhance inducing macrophages, well promote malignant glioblastoma. Targeting may serve a potential target against
Язык: Английский
Процитировано
6
Molecular Oncology, Год журнала: 2024, Номер unknown
Опубликована: Май 7, 2024
Glioblastoma is the most common primary malignant tumour of central nervous system and remains uniformly rapidly fatal. The tumour‐associated macrophage (TAM) compartment comprises brain‐resident microglia bone marrow‐derived macrophages (BMDMs) recruited from periphery. Immune‐suppressive tumour‐supportive TAM cell states predominate in glioblastoma, immunotherapies, which have achieved striking success other solid tumours consistently failed to improve survival this ‘immune‐cold’ niche context. Hypoxic necrotic regions core are found enrich, especially anti‐inflammatory immune‐suppressive states. Microglia at invasive margin express pro‐inflammatory interferon signatures. Depletion TAMs, or repolarisation towards a state, appealing therapeutic strategies will depend on effective understanding classification ontogeny state based new single‐cell spatial multi‐omic situ profiling. Here, we explore application these datasets expand refine characterisation, inform improved modelling approaches, ultimately underpin manipulation function.
Язык: Английский
Процитировано
5
CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(7)
Опубликована: Июль 1, 2024
Abstract Introduction Glioblastoma (GBM) remains a challenging brain tumor to treat, with limited response PD‐1 immunotherapy due tumor‐associated macrophages (TAMs), specifically the M2 phenotype. This study explores potential of MS4A4A (membrane spanning four domains, subfamily A, member 4A) inhibition in driving macrophage polarization toward M1 phenotype via ferroptosis pathway enhance effectiveness GBM. Methods Single‐cell RNA sequencing and spatial transcriptomic analyses were employed characterize expression In vitro studies utilizing TAM cultures, flow cytometry, western blot validations conducted assess impact on immune microenvironment polarization. vivo models, including subcutaneous orthotopic transplantation mice, utilized evaluate effects knockout combined checkpoint blockade (ICB) therapy growth immunotherapy. Results Distinct subsets GBM‐associated identified, distribution tissue elucidated. experiments demonstrated that inhibiting combining ICB effectively inhibited growth, reshaped by reducing infiltration enhancing CD8 + T‐cell infiltration, ultimately leading complete eradication. Conclusion shows promise converting ferroptosis, decreasing M2‐TAM GBM These findings offer novel approach developing more effective immunotherapeutic strategies for
Язык: Английский
Процитировано
5