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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Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

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

Published: Feb. 22, 2024

Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of gastric mucosa. The pathogenesis GC intricately linked to tumor microenvironment within which reside. Tumor-associated macrophages (TAMs) primarily differentiate peripheral blood monocytes and can be broadly categorized into M1 M2 subtypes. M2-type TAMs have been shown promote growth, tissue remodeling, angiogenesis. Furthermore, they actively suppress acquired immunity, leading poorer prognosis reduced tolerance chemotherapy. Exosomes, contain myriad biologically active molecules including lipids, proteins, mRNA, noncoding RNAs, emerged as key mediators communication between TAMs. exchange these via exosomes markedly influence consequently impact progression. Recent studies elucidated correlation various clinicopathological parameters GC, such size, differentiation, infiltration depth, lymph node metastasis, TNM staging, highlighting pivotal role in development metastasis. In this review, we aim comprehensively examine bidirectional TAMs, implications alterations on immune escape, invasion, metastasis targeted therapeutic approaches for efficacy potential drug resistance strategies.

Language: Английский

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Advances in research on immune escape mechanism of glioma

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(7), P. 1709 - 1720

Published: April 23, 2023

Abstract Background Glioma is the most common primary intracranial malignancy in clinical practice, and particular, IDH‐wildtype glioblastoma has worst prognosis. In recent years, surgical resection combined with simultaneous radiotherapy immune checkpoint inhibitors made some progress, but efficacy still not satisfactory, which may be related to low immunogenicity of glioma cells tumor immunosuppressive microenvironment. Methods A comprehensive review relevant literature was conducted explore mechanisms by tumors suppress antitumor responses produce escape, a focus on microenvironment (TME). Results The involved evasion are complex involve cell differentiation function. Conclusion Our emphasizes need for more profound comprehension response glioma, formulate efficacious treatment modalities.

Language: Английский

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Advanced tumor electric fields therapy: A review of innovative research and development and prospect of application in glioblastoma

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(5)

Published: May 1, 2024

Abstract Background Glioblastoma multiforme (GBM) is an aggressive malignant tumor with a high mortality rate and the most prevalent primary intracranial that remains incurable. The current standard treatment, which involves surgery along concurrent radiotherapy chemotherapy, only yields survival time of 14–16 months. However, introduction electric fields therapy (TEFT) has provided glimmer hope for patients newly diagnosed recurrent GBM, as it been shown to extend median 20 combination TEFT other advanced therapies promising trend in field facilitated by advancements medical technology. Aims In this review, we provide concise overview mechanism efficacy TEFT. addition, mainly discussed innovation our proposed blueprint implementation. Conclusion Tumor effective highly treatment modality GBM. full therapeutic potential can be exploited combined innovative technologies treatments.

Language: Английский

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Immune cell infiltration and inflammatory landscape in primary brain tumours

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 30, 2024

Abstract Background Primary malignant brain tumours are more than one-third of all and despite the molecular investigation to identify cancer driver mutations, current therapeutic options available challenging due high intratumour heterogeneity. In addition, an immunosuppressive inflammatory tumour microenvironment strengthens progression. Therefore, we defined immune profiling meningioma glial elucidate role infiltration in these types. Methods Using tissue microarrays 158 samples, assessed CD3, CD4, CD8, CD20, CD138, Granzyme B (GzmB), 5-Lipoxygenase (5-LOX), Programmed Death-Ligand 1 (PD-L1), O-6-Methylguanine-DNA Methyltransferase (MGMT) Transglutaminase 2 (TG2) expression by immunohistochemistry (IHC). IHC results were correlated using a Spearman correlation matrix. Transcript expression, correlation, overall survival (OS) analyses evaluated public datasets on GEPIA2 Glioblastoma (GBM) Lower Grade Glioma (LGG) cohorts. Results Seven out ten markers showed significantly different at least one cohorts whereas CD4 5-LOX differentially expressed between GBMs astrocytomas. Correlation matrix analysis revealed that GzmB associated both meningiomas GBMs, was positively TG2 astrocytoma These findings confirmed with TCGA-GBM LGG datasets. Profiling mRNA levels indicated significant increase CD3 (CD3D, CD3E), CD138 (SDC1) GBM compared control tissues. (ALOX5) samples normal tissues LGG. cohort, (GZMB), SDC1 MGMT gene predicted poor (OS). Moreover, increased CD3E, CD3G), CD8 (CD8A), GZMB, CD20 (MS4A1), SDC1, PD-L1, ALOX5, (TGM2) genes worse OS. Conclusions Our data have there is positive GzmB, RNA protein level. Further evaluation needed understand interplay glioma

Language: Английский

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Insights of immune cell heterogeneity, tumor-initiated subtype transformation, drug resistance, treatment and detecting technologies in glioma microenvironment

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

With the gradual understanding of glioma development and immune microenvironment, many cells have been discovered. Despite growing comprehension cell functions clinical application immunotherapy, precise roles characteristics subtypes, how induces subtype transformation its impact on progression yet to be understood. In this review, we comprehensively center four major within particularly neutrophils, macrophages, lymphocytes, myeloid-derived suppressor (MDSCs), other significant cells. We discuss (1) markers, (2) glioma-induced transformation, (3) mechanisms each influencing chemotherapy resistance, (4) therapies targeting cells, (5) cell-associated single-cell sequencing. Eventually, identified subtypes in glioma, summarized exact mechanism concluded progress sequencing exploring glioma. conclusion, analyzed resistance detailly, discovered prospective immunotherapy targets, excavating potential novel immunotherapies approach that synergistically combines radiotherapy, chemotherapy, surgery, thereby paving way for improved immunotherapeutic strategies against enhanced patient outcomes.

Language: Английский

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Identification of Key Immune and Cell Cycle Modules and Prognostic Genes for Glioma Patients through Transcriptome Analysis

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(10), P. 1295 - 1295

Published: Sept. 28, 2024

Background: Gliomas, the most prevalent type of primary brain tumor, stand out as one aggressive and lethal types human cancer. Methods & Results: To uncover potential prognostic markers, we employed weighted correlation network analysis (WGCNA) on Chinese Glioma Genome Atlas (CGGA) 693 dataset to reveal four modules significantly associated with glioma clinical traits, primarily involved in immune function, cell cycle regulation, ribosome biogenesis. Using least absolute shrinkage selection operator (LASSO) regression algorithm, identified 11 key genes developed a risk score model, which exhibits precise prediction CGGA 325 dataset. More importantly, also validated model 12 patients overall survival (OS) ranging from 4 132 months using mRNA sequencing immunohistochemical analysis. The infiltration revealed that high-risk scores exhibit heightened infiltration, particularly suppression cells, along increased expression checkpoints. Furthermore, explored potentially effective drugs targeting for gliomas library integrated network-based cellular signatures (LINCS) L1000 database, identifying vitro, both torin-1 clofarabine promising anti-glioma activity inhibitory effect cycle, significant pathway enriched modules. Conclusions: In conclusion, our study provides valuable insights into molecular mechanisms therapeutic targets gliomas.

Language: Английский

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BRD4 promotes immune escape of glioma cells by upregulating PD-L1 expression

Journal of Neuro-Oncology, Journal Year: 2024, Volume and Issue: 171(3), P. 669 - 679

Published: Nov. 28, 2024

Language: Английский

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Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 15, 2023

Glioblastoma (GBM) is notorious for its clinical and molecular heterogeneity, contributing to therapeutic failure a grim prognosis. WWOX one of the tumor suppressor genes important in nervous tissue or related pathologies, which was scarcely investigated GBM reliable associations with prognosis disease progression despite known alterations. Recently, we observed phenotypic heterogeneity between cell lines (U87MG, T98G, U251MG, DBTRG-05MG), among anti-GBM activity generally corresponding, but colony growth formation were inconsistent DBTRG-05MG. This prompted us investigate landscapes these lines, intending translate them into context.U87MG/T98G/U251MG/DBTRG-05MG subjected high-throughput sequencing, obtained data explored via weighted gene co-expression network analysis, differential expression functional annotation, building. Following identification most relevant DBTRG-distinguishing driver genes, from patients employed for, e.g., survival principal component analysis.Although unique each line, some inversely regulated Alongside differentially-expressed used build WWOX-related depicting protein-protein interactions U87MG/T98G/U251MG/DBTRG-05MG. revealed processes distinctly DBTRG-05MG, microglia proliferation neurofibrillary tangle assembly. POLE4 HSF2BP selected as DBTRG-discriminating based on significance, module membership, fold-change. WWOX, stratify lines-resembling groups that differed in, treatment response. Some differences certified patients, revealing clarify outcomes. Presumably, overexpression DBTRG-05MG resulted profile change resembling inferior drug Among may be inaccessible partners does not manifest anti-cancer activity, proposed literature regarding glioblastoma concerning HSF2BP.Cell enabled which, high suppressor, no advantageous outcomes noted due cancer-promoting ensured by other genes.

Language: Английский

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Detailed pathological role of non-coding RNAs (ncRNAs) in regulating drug resistance of glioblastoma; and update

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 263, P. 155590 - 155590

Published: Sept. 12, 2024

Language: Английский

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