Unlocking the Code: The Role of Molecular and Genetic Profiling in Revolutionizing Glioblastoma Treatment DOI Creative Commons
Moustafa Mansour,

Ahmed M Kamer-Eldawla,

Reem W Malaeb

et al.

Cancer Treatment and Research Communications, Journal Year: 2024, Volume and Issue: 43, P. 100881 - 100881

Published: Jan. 1, 2024

Glioblastoma (GBM) is the most aggressive primary brain cancer, characterized by profound molecular and cellular heterogeneity, which contributes to its resistance conventional therapies poor prognosis. Despite multimodal treatments including surgical resection, radiation, chemotherapy, median survival remains approximately 15 months. Recent advances in genetic profiling have elucidated key alterations subtypes of GBM, such as EGFR amplification, PTEN ATRX loss, TP53 alterations, significant prognostic therapeutic implications. These discoveries spurred development targeted aimed at disrupting aberrant signaling pathways like RTK/RAS/PI3K TP53. However, treatment a formidable challenge, driven tumor complex microenvironment (TME), intrinsic adaptive mechanisms. Emerging approaches aim address these challenges, use immunotherapies immune checkpoint inhibitors CAR T-cell therapies, target specific antigens but face hurdles due immunosuppressive TME. Additionally, novel strategies biopolymer-based interstitial focused ultrasound for blood-brain barrier disruption, nanoparticle-based drug delivery systems show promise enhancing efficacy precision GBM treatments. This review explores evolving landscape therapy, emphasizing importance personalized medicine through profiling, potential combination need innovative overcome resistance. Continued research into GBM's biology modalities offers hope improving patient outcomes.

Language: Английский

CD4+ T cells in antitumor immunity DOI Creative Commons
Elena Montauti, David Y. Oh, Lawrence Fong

et al.

Trends in cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

11
GBM immunotherapy: Exploring molecular and clinical frontiers DOI
Mrinal K. Ghosh,

Sunny Kumar,

Sabana Begam

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 356, P. 123018 - 123018

Published: Aug. 28, 2024

Language: Английский

Citations

5
Investigation of the Impact of Magnetic Resonance Imaging-assisted Surgery on Immune Cell Cytokine Levels and Efficacy in Patients with Gliomas DOI Creative Commons

Xueshan Qian,

Li Yang,

Yonghui Shi

et al.

Current Problems in Surgery, Journal Year: 2024, Volume and Issue: 63, P. 101640 - 101640

Published: Oct. 18, 2024

Language: Английский

Citations

4
Emerging Mechanisms and Biomarkers Associated with T-Cells and B-Cells in Autoimmune Disorders DOI
Azhagu Madhavan Sivalingam

Clinical Reviews in Allergy & Immunology, Journal Year: 2025, Volume and Issue: 68(1)

Published: Feb. 11, 2025

Language: Английский

Citations

0
Prognostic Biomarkers in Isocitrate Dehydrogenase Wild-Type Glioblastoma: A Focus on B7-H3 DOI Creative Commons
Ramazan Oğuz Yüceer, Şeyhmus Kaya, Şenay Balcı

et al.

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(2), P. 212 - 212

Published: Feb. 19, 2025

Isocitrate dehydrogenase (IDH) wild-type (wt) glioblastoma is an aggressive malignancy associated with poor clinical outcomes, marked by high heterogeneity and resistance to treatment. This study aims investigate the prognostic significance of B7-H3 expression in IDH wt its potential association including overall survival (OS) progression-free (PFS). Additionally, relationship between PD-L1 was explored. A retrospective cohort 86 patients, all whom underwent surgery, radiotherapy, temozolomide treatment, analyzed. quantified using immunoreactivity score (IRS), classifying samples as low (IRS ≤ 4) or > 4). evaluated based on tumor immune cell staining, >5% positivity indicating significant expression. High significantly poorer OS PFS. Co-expression prevalent, particularly among younger male patients unifocal tumors; however, did not show a correlation outcomes. appears be promising biomarker may serve target for developing combination therapies, integrating B7-H3-targeting treatments checkpoint inhibitors. Further prospective studies are necessary validate these findings explore therapeutic strategies.

Language: Английский

Citations

0
Integrated Analysis to Reveal Heterogeneity of Tumor‐Associated Neutrophils in Glioma DOI Creative Commons
Wen Wang, Junsheng Li, Qiheng He

et al.

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(5)

Published: March 1, 2025

Glioma, characterized by its cellular and molecular heterogeneity, presents formidable challenges in treatment strategy prognostic assessment. The tumor microenvironment (TME) profoundly influences behavior response, with tumor-associated neutrophils (TANs) playing a complex but understudied role. This study aimed to investigate the heterogeneity role of TANs glioma develop model. Analysis scRNA-seq data identified subpopulations differentially expressed neutrophil-related genes (DE-NRGs). Bulk RNA-seq was obtained from four independent datasets. Molecular subtypes samples were determined consensus clustering. WGCNA conducted elucidate association between gene modules subtypes. We developed risk score Expression selected confirmed using immunohistochemistry (IHC). In vitro experiments also performed for functional verification, including CCK8, EdU, Transwell, TUNEL assays. A total 108 DE-NRGs based on data. Two characterized, showing significant differences prognosis clinical features. Immune-related analyses demonstrated varied immunological characteristics model constructed 7 genes, AEBP1, CAVIN1, DCTD, DEPP1, DUSP6, FKBP9, UGCG. It showed value validated across three external mutation landscape highlighted higher IDH prevalence low-risk groups. Drug sensitivity analysis indicated TMZ resistance high-risk that UGCG could promote cell proliferation, migration, invasion, while decreasing apoptosis. explored model, providing insights prediction guiding personalized strategies glioma. Declaration Generative AI Scientific Writing: authors declare nonuse generative AI-assisted technologies writing process.

Language: Английский

Citations

0
Role of T Lymphocytes in Glioma Immune Microenvironment: Two Sides of a Coin DOI Creative Commons

Lubna Noor,

Arun Upadhyay, Vibhuti Joshi

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(10), P. 846 - 846

Published: Oct. 21, 2024

Glioma is known for its immunosuppressive microenvironment, which makes it challenging to target through immunotherapies. Immune cells like macrophages, microglia, myeloid-derived suppressor cells, and T lymphocytes are infiltrate the glioma tumor microenvironment regulate immune response distinctively. Among variety of have highly complex multifaceted roles in landscape. lymphocytes, include CD4+ helper CD8+ cytotoxic their pivotal anti-tumor responses. However, these may behave differently dynamic example, via an invasion mechanism enforced by cells. Therefore, play dual immunity, firstly responses, secondly exploiting gliomas promote invasion. As immunosuppression strategy, induces T-cell exhaustion suppression effector regulatory (Tregs) or altering signaling pathways. Further, expression checkpoint inhibitors on cell surface leads anergy dysfunction. Overall, this interplay between crucial designing more effective The current review provides detailed knowledge helps explore novel therapeutic approaches reinvigorate lymphocytes.

Language: Английский

Citations

3
Immune cell infiltration and inflammatory landscape in primary brain tumours DOI Creative Commons
Amalia Luce, Marianna Abate, Giosuè Scognamiglio

et al.

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

Citations

2
A comprehensive neuroimaging review of the primary and metastatic brain tumors treated with immunotherapy: current status, and the application of advanced imaging approaches and artificial intelligence DOI Creative Commons
Xuwen Liu, Hongyan Chen, Guirong Tan

et al.

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

Published: Nov. 28, 2024

Cancer immunotherapy has emerged as a novel clinical therapeutic option for variety of solid tumors over the past decades. The application in primary and metastatic brain continues to grow despite limitations due physiological characteristics immune system within central nervous (CNS) distinct pathological barriers malignant tumors. post-immunotherapy treatment imaging is more complex. In this review, we summarize immunotherapies beyond CNS. We provide an overview current used tumors, including checkpoint inhibitors (ICIs), oncolytic viruses, vaccines, CAR T-cell therapies. focus on criteria assessment response immunotherapy, patterns. discuss advanced techniques evaluation treatment-related complications CNS are described. Lastly, future challenges field explored.

Language: Английский

Citations

1
CDC6 overexpression contributes to the malignant phenotype of glioma via IL6/JAK2/STAT3 signaling DOI
Hao Zhao,

Hu Sun,

Jing‐Yuan Fang

et al.

American Journal of Cancer Research, Journal Year: 2024, Volume and Issue: 14(7), P. 3372 - 3387

Published: Jan. 1, 2024

Glioma, a prevalent primary tumor of the central nervous system, is targeted by molecular therapies aiming to intervene in specific genes and signaling pathways inhibit growth spread. Our previous bioinformatics study revealed that significant CDC6 overexpression gliomas was closely correlated with poor patient prognosis. Through qPCR, western blotting, immunohistochemistry, we will further validate expression clinical glioma specimens, while effects silencing overexpressing U87 LN229 cell lines on malignancy be assessed through MTS, EdU, transwell, migration assays. Luciferase reporter assays, ChIP, blotting were used explore upstream downstream mechanisms CDC6. confirmed abnormal gliomas, particularly glioblastomas. promotes activity, proliferation, invasion, activating IL6-mediated JAK2/STAT3 pathway. The transcription Factor E2F8 directly regulates transcription, playing crucial role its gliomas. This research provides vital evidence supporting as target for therapy.

Language: Английский

Citations

0