Spatial biology – unravelling complexity within the glioblastoma microenvironment

Trends in Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

HighlightsThe ability to understand molecular differences at a single cell level, and with increasing granularity, through spatial profiling is starting unravel the complexity of glioblastoma tumour microenvironment (TME).Identifying variations in distribution different types providing novel insights into biology leading identification TME-based subtypes.Greater understanding relationships between types, rare, but biologically important, states identifying new biomarkers for predicting an individual's response treatment suggesting resistance mechanisms.AbstractThe advent refinement state-of-the-art technologies have facilitated analysis that combines advantages high-throughput techniques preserve tissue architecture. This combination cellular phenotyping retained context provides much greater interactions within (TME). For glioblastoma, its significant intra-tumoural heterogeneity, plasticity, complex TME, appreciating these patterns may prove key improving patient outcomes. review examines advances techniques, discusses how methodologies are being applied study explores information improves TME. Ultimately, it this will accelerate more effective treatments glioblastoma.

Language: Английский

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Tackling Prostate Cancer with Theranostic E5B9-Bombesin Target Modules (TMs): From Imaging to Treatment with UniCAR T-Cells

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2686 - 2686

Published: March 17, 2025

Target modules (TMs), intermediate molecules required for UniCAR T-cell therapy, are promising immunotheranostic approaches. In the current work, we developed TMs containing a monomeric or dimeric form of antagonist bombesin peptide (BBN2) and assessed their potential diagnostic imaging using positron emission tomography (PET) as well immunotherapy in combination with T-cells to target image GRPR expression prostate cancer. Synthesized BBN2 retained binding vitro. Both specifically activated redirected eradicate PC3 LNCaP cancer cells high efficiency comparable manner. non-exhausted memory phenotype favorable persistence fitness. The 68Ga-labeled showed proof-of-target towards xenografts similar uptake profiles both dynamic PET experiments. Clearance occurred exclusively through renal elimination. A tremendously increased vivo metabolic stability was observed compared counterparts without E5B9. represent novel tools application exceptionally stability.

Language: Английский

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Harnessing Immune Rejuvenation: Advances in Overcoming T Cell Senescence and Exhaustion in Cancer Immunotherapy

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Immunotherapy has transformed the landscape of cancer treatment, with T cell-based strategies at forefront this revolution. However, durability these responses is frequently undermined by two intertwined phenomena: cell exhaustion and senescence. While driven chronic antigen exposure in immunosuppressive tumor microenvironment, leading to a reversible state diminished functionality, senescence reflects more permanent, age- or stress-induced arrest cellular proliferation effector capacity. Together, processes represent formidable barriers sustained anti-tumor immunity. In review, we dissect molecular underpinnings senescence, revealing how dysfunctions synergistically contribute immune evasion resistance across range solid tumors. We explore cutting-edge therapeutic approaches aimed rewiring exhausted senescent phenotypes. These include advances checkpoint blockade, engineering "armored" CAR-T cells, senolytic therapies that selectively eliminate novel interventions reinvigorate system's capacity for eradication. By spotlighting emerging target both provide forward-looking perspective on potential harness rejuvenation. This comprehensive review outlines next frontier immunotherapy: unlocking durable overcoming intrinsic aging exhaustion, ultimately paving way transformative breakthroughs.

Language: Английский

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Multi-disciplinary approaches paving the way for clinically effective peptide vaccines for cancer

npj Vaccines, Journal Year: 2025, Volume and Issue: 10(1)

Published: April 9, 2025

Abstract Cytotoxic CD8 + T lymphocyte (CTL) cells are central in mediating antitumor immunity. Induction of a robust CTL response requires, interaction with professional antigen-presenting cells, such as dendritic displaying onco-antigenic peptide, often derived from tumor-associated antigens (TAAs) or neoantigens, and costimulation via CD4 helper which then elicits an effector memory immune that targets kills cancer cells. Despite the tumoricidal capacity CTLs, can escape surveillance killing due to their immunosuppressive tumor microenvironment (TME). Therefore, harness combat effect TME, peptide-based cell vaccines targeting specific onco-antigens, conjugated adjuvants subject ongoing research for immunotherapy; particularly, multi-peptide vaccines, containing both epitopes along immunostimulant. Historically, have been investigated potential strategy immunotherapy. initial enthusiasm, these peptide not demonstrated success clinical outcomes. However, recent advancements our understanding immunology design paved way novel strategies These reignited optimism surrounding viable therapeutic. This review explores new discusses exciting possibilities they offer. Specifically, this develops vaccine outcomes, by discussing mechanisms responses, how induce enhance responses. It addresses challenge Major Histocompatibility Complex (MHC) restriction, limits effectiveness traditional individuals diverse MHC types. also delves into overcoming its inhibitory effects using efficient elimination. The aims provide complexities faced each field design, enhancing dialogue among researchers bringing together chemistry synthesis, immunology, studies support development vaccine.

Language: Английский

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Molecular insight into T cell exhaustion in hepatocellular carcinoma

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107161 - 107161

Published: March 29, 2024

Hepatocellular carcinoma is one of leading causes cancer-related mortality globally. The emergence immunotherapy has been shown to be a promising therapeutic approach for hepatocellular in recent years. It well known that T cells play key role current immunotherapy. However, sustained exposure antigenic stimulation within the tumor microenvironment may lead cell exhaustion, which cause treatment ineffectiveness. Therefore, reversing exhaustion an important issue clinical application immunotherapy, and comprehensive understanding intricacies surrounding its underlying mechanisms imperative devising strategies overcome during treatment. In this review, we summarized reported drivers delineate potential ways reverse it. Additionally, discussed interplay among metabolic plasticity, epigenetic regulation, transcriptional factors exhausted carcinoma, their implication future applications.

Language: Английский

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