Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

Cancer Cell, Год журнала: 2021, Номер 39(6), С. 779 - 792.e11

Опубликована: Июнь 1, 2021

Язык: Английский

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The implications of IDH mutations for cancer development and therapy

Nature Reviews Clinical Oncology, Год журнала: 2021, Номер 18(10), С. 645 - 661

Опубликована: Июнь 15, 2021

Язык: Английский

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Frontiers in the treatment of glioblastoma: Past, present and emerging

Advanced Drug Delivery Reviews, Год журнала: 2021, Номер 171, С. 108 - 138

Опубликована: Янв. 22, 2021

Язык: Английский

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CXCL11-armed oncolytic adenoviruses enhance CAR-T cell therapeutic efficacy and reprogram tumor microenvironment in glioblastoma

Molecular Therapy, Год журнала: 2022, Номер 31(1), С. 134 - 153

Опубликована: Сен. 2, 2022

Glioblastoma (GBM) is the most aggressive primary malignant brain cancer and urgently requires effective treatments. Chimeric antigen receptor T (CAR-T) cell therapy offers a potential treatment method, but it often hindered by poor infiltration of CAR-T cells in tumors highly immunosuppressive tumor microenvironment (TME). Here, we armed an oncolytic adenovirus (oAds) with chemokine CXCL11 to increase reprogram TME, thus improving its therapeutic efficacy. In both immunodeficient immunocompetent orthotopic GBM mice models, showed that B7H3-targeted alone failed inhibit growth but, when combined intratumoral administration CXCL11-armed oAd, achieved durable antitumor response. Besides, oAd-CXCL11 had potent effect reprogramed TME GL261 which increased CD8+ lymphocytes, natural killer (NK) cells, M1-polarized macrophages, while decreased proportions myeloid-derived suppressor (MDSCs), regulatory (Tregs) M2-polarized macrophages were observed. Furthermore, was dependent. Our findings revealed oAd can improve immune-virotherapy be promising adjuvant for GBM.

Язык: Английский

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Allogeneic CAR T Cells: An Alternative to Overcome Challenges of CAR T Cell Therapy in Glioblastoma

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Март 3, 2021

Chimeric antigen receptor (CAR) T cell therapy has emerged as one of the major breakthroughs in cancer immunotherapy last decade. Outstanding results hematological malignancies and encouraging pre-clinical anti-tumor activity against a wide range solid tumors have made CAR cells most promising fields for therapies. is currently being investigated including glioblastoma (GBM), tumor which survival only modestly improved over past decades. targeting EGFRvIII, Her2, or IL-13Rα2 been tested GBM, but first clinical trials shown modest results, potentially due to GBM heterogeneity presence an immunosuppressive microenvironment. Until now, use autologous manufacture products norm, this approach several disadvantages regarding production time, cost, manufacturing delay dependence on functional fitness patient cells, often reduced by disease previous Universal “off-the-shelf,” allogeneic, alternative that can overcome these issues, allow multiple modifications combinations target antigens avoid escape. Advances genome editing tools, especially via CRISPR/Cas9, might overcoming two main limitations allogeneic product, i.e., graft-vs.-host host allorejection. Here, we will discuss how could multivalent approaches alteration microenvironment, allowing development next generation therapies treatment patients with GBM.

Язык: Английский

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Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Май 8, 2024

Abstract Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, exploration of emerging modalities such as immunotherapy integration medicine engineering technology therapy, efficacy these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny inhibitory milieu within GBM has underscored significance cellular constituents microenvironment their interactions with cells neurons. Novel immune targeted therapy strategies have emerged, offering promising avenues for advancing treatment. One pivotal mechanism orchestrating immunosuppression involves aggregation myeloid-derived suppressor (MDSCs), glioma-associated macrophage/microglia (GAM), regulatory T (Tregs). Among these, MDSCs, though constituting minority (4–8%) CD45 + GBM, play central component fostering evasion propelling tumor progression, angiogenesis, invasion, metastasis. MDSCs deploy intricate mechanisms that adapt dynamic (TME). Understanding interplay between provides compelling basis This review seeks elucidate inherent explore existing targets, consolidate insights into MDSC induction contribution immunosuppression. Additionally, comprehensively surveys ongoing clinical trials potential strategies, envisioning future where targeting could reshape landscape GBM. Through synergistic other modalities, this approach can establish multidisciplinary, multi-target paradigm, ultimately improving prognosis quality life patients

Язык: Английский

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Tailoring vascular phenotype through AAV therapy promotes anti-tumor immunity in glioma

Cancer Cell, Год журнала: 2023, Номер 41(6), С. 1134 - 1151.e10

Опубликована: Май 11, 2023

Glioblastomas are aggressive brain tumors that largely immunotherapy resistant. This is associated with immunosuppression and a dysfunctional tumor vasculature, which hinder T cell infiltration. LIGHT/TNFSF14 can induce high endothelial venules (HEVs) tertiary lymphoid structures (TLS), suggesting its therapeutic expression could promote recruitment. Here, we use cell-targeted adeno-associated viral (AAV) vector to express LIGHT in the glioma vasculature (AAV-LIGHT). We found systemic AAV-LIGHT treatment induces tumor-associated HEVs cell-rich TLS, prolonging survival αPD-1-resistant murine glioma. reduces exhaustion promotes TCF1+CD8+ stem-like cells, reside TLS intratumoral antigen-presenting niches. Tumor regression upon therapy correlates tumor-specific cytotoxic/memory responses. Our work reveals altering vascular phenotype through vessel-targeted of efficient anti-tumor responses prolongs These findings have broader implications for other immunotherapy-resistant cancers.

Язык: Английский

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Glioblastoma Therapy: Past, Present and Future

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2529 - 2529

Опубликована: Фев. 21, 2024

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians researchers, no significant improvement in survival has achieved since Stupp protocol became standard care (SOC) 2005. Despite multimodality treatments, recurrence is almost universal with rates under 2 years after diagnosis. Here, we discuss recent progress our understanding GB pathophysiology, particular, importance glioma stem cells (GSCs), tumor microenvironment conditions, epigenetic mechanisms involved growth, aggressiveness recurrence. The discussion on therapeutic strategies first covers SOC treatment targeted therapies that shown to interfere different signaling pathways (pRB/CDK4/RB1/P16

Язык: Английский

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Recent Developments in Glioblastoma Therapy: Oncolytic Viruses and Emerging Future Strategies

Viruses, Год журнала: 2023, Номер 15(2), С. 547 - 547

Опубликована: Фев. 16, 2023

Glioblastoma is the most aggressive form of malignant brain tumor. Standard treatment protocols and traditional immunotherapy are poorly effective as they do not significantly increase long-term survival glioblastoma patients. Oncolytic viruses (OVs) may be an alternative approach. Combining OVs with some modern options also provide significant benefits for Here we review virotherapy glioblastomas describe several their combination other therapies. The personalized use would become a area research aiming to develop regimens glioblastomas.

Язык: Английский

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Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications

Cancers, Год журнала: 2021, Номер 13(16), С. 4226 - 4226

Опубликована: Авг. 23, 2021

Gliomas are the most common, highly malignant, and deadliest forms of brain tumors. These intra-cranial solid tumors comprised both cancerous non-cancerous cells, which contribute to tumor development, progression, resistance therapeutic regimen. A variety soluble inflammatory mediators (e.g., cytokines, chemokines, chemotactic factors) secreted by these help in creating an microenvironment various stages cancer maintenance, progression. The major infiltrating immune cells include TAMs TANs, either recruited peripherally or present as brain-resident macrophages (microglia) support stroma for cell expansion invasion. plastic nature can be polarized into different phenotypes depending upon types stimuli. During neuroinflammation, glioma interact with facilitating proliferation, survival, migration. Targeting along reprogramming TANs could great importance treatment may delay disease In addition, inhibition key signaling pathways such NF-κB, JAK/STAT, MAPK, PI3K/Akt/mTOR, TLRs, activated during neuroinflammation have oncogenic role glioblastoma (GBM), exert more pronounced anti-glioma effects.

Язык: Английский

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