Exosomal circRNA: emerging insights into cancer progression and clinical application potential

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: June 26, 2023

Abstract Exosomal circRNA serves a novel genetic information molecule, facilitating communication between tumor cells and microenvironmental cells, such as immune fibroblasts, other components, thereby regulating critical aspects of cancer progression including escape, angiogenesis, metabolism, drug resistance, proliferation metastasis. Interestingly, microenvironment have new findings in influencing escape mediated by the release exosomal circRNA. Given intrinsic stability, abundance, broad distribution circRNAs, they represent excellent diagnostic prognostic biomarkers for liquid biopsy. Moreover, artificially synthesized circRNAs may open up possibilities therapy, potentially bolstered nanoparticles or plant exosome delivery strategies. In this review, we summarize functions underlying mechanisms cell non-tumor cell-derived progression, with special focus on their roles immunity metabolism. Finally, examine potential application therapeutic targets, highlighting promise clinical use.

Language: Английский

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Peritumoral brain zone in glioblastoma: biological, clinical and mechanical features

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

Published: Feb. 29, 2024

Glioblastoma is a highly aggressive and invasive tumor that affects the central nervous system (CNS). With five-year survival rate of only 6.9% median time eight months, it has lowest among CNS tumors. Its treatment consists surgical resection, subsequent fractionated radiotherapy concomitant adjuvant chemotherapy with temozolomide. Despite implementation clinical interventions, recurrence common occurrence, over 80% cases arising at edge resection cavity few months after treatment. The high location glioblastoma indicate need for better understanding peritumor brain zone (PBZ). In this review, we first describe main radiological, cellular, molecular biomechanical tissue features PBZ; subsequently, discuss its current management, potential local therapeutic approaches future prospects.

Language: Английский

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Glioblastoma-Infiltrating CD8+ T Cells Are Predominantly a Clonally Expanded GZMK+ Effector Population

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(6), P. 1106 - 1131

Published: Feb. 27, 2024

Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy in patients with glioblastoma (GBM). To better understand characteristics tumor-infiltrating lymphocytes (TIL) GBM, we performed cellular indexing transcriptomes and epitopes by sequencing single-cell RNA paired V(D)J sequencing, respectively, on TILs from two cohorts totaling 15 high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis CD8+ TIL landscape reveals an enrichment clonally expanded GZMK+ effector cells tumor compared matched blood, which was validated at protein level. Furthermore, integration other cancer types highlights lack a canonically exhausted T-cell population TIL. These data suggest that represent important subset within microenvironment may harbor potential therapeutic implications.

Language: Английский

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Immunoregulatory role of exosomal circRNAs in the tumor microenvironment

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

Published: Feb. 17, 2025

As cancer incidence and mortality rates rise, there is an urgent need to develop effective immunotherapy strategies. Circular RNA (circRNA), a newly identified type of non-coding RNA, abundant within cells can be released via exosomes, facilitating communication between cells. Studies have demonstrated that exosomal circRNAs alter the tumor microenvironment modulate immune responses by influencing functions T cells, natural killer (NK) macrophages, thereby enabling tumors evade system. Moreover, show potential as diagnostic biomarkers therapeutic targets for cancer. This review summarizes regulatory roles in their applications progression treatment, highlighting promise improving immunotherapy. Future research should concentrate on understanding mechanisms key developing targeted methods.

Language: Английский

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Immunity/metabolism dual-regulation via an acidity-triggered bioorthogonal assembly nanoplatform enhances glioblastoma immunotherapy by targeting CXCL12/CXCR4 and adenosine-A2AR pathways

Biomaterials, Journal Year: 2025, Volume and Issue: 319, P. 123216 - 123216

Published: Feb. 26, 2025

Language: Английский

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rWTC‐MBTA Vaccine Induces Potent Adaptive Immune Responses Against Glioblastomas via Dynamic Activation of Dendritic Cells

Advanced Science, Journal Year: 2024, Volume and Issue: 11(14)

Published: Jan. 31, 2024

Abstract Despite strides in immunotherapy, glioblastoma multiforme (GBM) remains challenging due to low inherent immunogenicity and suppressive tumor microenvironment. Converting “cold” GBMs “hot” is crucial for immune activation improved outcomes. This study comprehensively characterized a therapeutic vaccination strategy preclinical GBM models. The vaccine consists of Mannan‐BAM‐anchored irradiated whole cells, Toll‐like receptor ligands [lipoteichoic acid (LTA), polyinosinic‐polycytidylic (Poly (I:C)), resiquimod (R‐848)], anti‐CD40 agonistic antibody (rWTC‐MBTA). Intracranial models (GL261, SB28 cells) are used evaluate the efficacy. A substantial number vaccinated mice exhibited complete regression tumors T‐cell‐dependent manner, with no significant toxicity. Long‐term tumor‐specific memory confirmed upon rechallenge. In vaccine‐draining lymph nodes model, rWTC‐MBTA triggered major rise conventional dendritic cell type 1 (cDC1) 12 h post‐treatment, followed by an increase 2 (cDC2), monocyte‐derived (moDC), plasmacytoid (pDC) on Day 5 13. Enhanced cytotoxicity CD4+ CD8+ T cells verified co‐culture cells. Analyses immunosuppressive signals (T‐cell exhaustion, myeloid‐derived suppressor (MDSC), M2 macrophages) microenvironment suggest potential combinations other immunotherapies enhanced conclusion, authors findings demonstrate that induces potent long‐term adaptive responses against GBM.

Language: Английский

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The need for paradigm shift: prognostic significance and implications of standard therapy-related systemic immunosuppression in glioblastoma for immunotherapy and oncolytic virotherapy

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

Published: Feb. 8, 2024

Despite significant advances in our knowledge regarding the genetics and molecular biology of gliomas over past two decades hundreds clinical trials, no effective therapeutic approach has been identified for adult patients with newly diagnosed glioblastoma, overall survival remains dismal. Great hopes are now placed on combination immunotherapy. In immunotherapeutics generally tested after standard therapy (radiation, temozolomide, steroid dexamethasone) or concurrently temozolomide and/or steroids. Only a minor subset progressive/recurrent glioblastoma have benefited from immunotherapies. this review, we comprehensively discuss therapy-related systemic immunosuppression lymphopenia, their prognostic significance, implications immunotherapy/oncolytic virotherapy. The effectiveness immunotherapy oncolytic virotherapy (viro-immunotherapy) critically depends activity host immune cells. absolute counts, ratios, functional states different circulating tumor-infiltrating cell subsets determine net fitness cancer may various effects tumor progression, response, outcomes. Although immunosuppressive mechanisms operate glioblastoma/gliomas at presentation, immunological competence be significantly compromised by therapy, exacerbating tumor-related immunosuppression. Standard affects diverse subsets, including dendritic, CD4+, CD8+, natural killer (NK), NKT, macrophage, neutrophil, myeloid-derived suppressor (MDSC). Systemic lymphopenia limit system’s ability to target glioblastoma. Changes required increase success Steroid use, high neutrophil-to-lymphocyte ratio (NLR), low post-treatment total lymphocyte count (TLC) factors shorter retrospective studies; however, these clinically relevant variables rarely reported correlated response studies (e.g., checkpoint inhibitors, vaccines, viruses). Our analysis should help development more rational trial design decision-making treatment potentially improve efficacy

Language: Английский

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Systemic and local immunosuppression in glioblastoma and its prognostic significance

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

Published: Feb. 28, 2024

The effectiveness of tumor therapy, especially immunotherapy and oncolytic virotherapy, critically depends on the activity host immune cells. However, various local systemic mechanisms immunosuppression operate in cancer patients. Tumor-associated involves deregulation many components immunity, including a decrease number T lymphocytes (lymphopenia), an increase levels or ratios circulating tumor-infiltrating immunosuppressive subsets [e.g., macrophages, microglia, myeloid-derived suppressor cells (MDSCs), regulatory (Tregs)], as well defective functions antigen-presenting, helper effector cell due to altered expression soluble membrane proteins (receptors, costimulatory molecules, cytokines). In this review, we specifically focus data from patients with glioblastoma/glioma before standard chemoradiotherapy. We discuss glioblastoma-related at baseline prognostic significance different (lymphocytes, CD4+ CD8+ cells, Tregs, natural killer (NK) neutrophils, MDSCs, dendritic cells), neutrophil-to-lymphocyte ratio (NLR), landscape isocitrate dehydrogenase ( IDH )-mutant gliomas, proneural, classical mesenchymal molecular subtypes, highlight features surveillance brain. All attempts identify reliable marker glioblastoma tissue have led contradictory results, which can be explained, among other things, by unprecedented level spatial heterogeneity infiltrate significant phenotypic diversity (dys)functional states subpopulations. High NLR is one most repeatedly confirmed independent factors for shorter overall survival carcinoma, its combination markers response inflammation significantly improves accuracy prediction; however, more prospective studies are needed confirm prognostic/predictive power NLR. call inclusion dynamic assessment blood inflammatory (e.g., absolute/total lymphocyte count, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte immune-inflammation index, index) all neuro-oncology rigorous evaluation comparison their individual combinatorial relative superiority.

Language: Английский

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Recent Advances in Biomimetic Strategies for the Immunotherapy of Glioblastoma

Biomaterials, Journal Year: 2024, Volume and Issue: 311, P. 122694 - 122694

Published: June 28, 2024

Language: Английский

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CTHRC1+ fibroblasts and SPP1+ macrophages synergistically contribute to pro-tumorigenic tumor microenvironment in pancreatic ductal adenocarcinoma

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 29, 2024

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal cancer that accounts for over 90% of all pancreatic cases. With a 5-year survival rate only 13%, PDAC has proven to be desmoplastic and immunosuppressive most current therapies, including chemotherapy surgical resection. In recent years, focus shifted understanding the tumor microenvironment (TME) around PDAC, enabling greater biological pathways intercellular interactions can ultimately lead potential future drug targets. this study, we leverage combination single-cell spatial transcriptomics further identify cellular populations within highly heterogeneous TME. We demonstrate SPP1

Language: Английский

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