PD1-TLR10 fusion protein enhances the antitumor efficacy of CAR-T cells in colon cancer

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114083 - 114083

Published: Jan. 15, 2025

Language: Английский

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Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12848 - 12848

Published: Nov. 29, 2024

This review explores some of the complex mechanisms underlying antitumor T-cell response, with a specific focus on balance and cross-talk between selected co-stimulatory inhibitory pathways. The tumor microenvironment (TME) fosters both activation exhaustion, dual role influenced by local presence immune checkpoints (ICs), which are exploited cancer cells to evade surveillance. Recent advancements in IC blockade (ICB) therapies have transformed treatment. However, only fraction patients respond favorably, highlighting need for predictive biomarkers combination overcome ICB resistance. A crucial aspect is represented complexity TME, encompasses diverse cell types that either enhance or suppress responses. underscores importance identifying most critical molecules developing approaches tailored patient-specific molecular profiles maximize therapeutic efficacy inhibitors clinical outcomes.

Language: Английский

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Aspalathin, a key flavonoid in rooibos, restores STAT6-mediated immune dysregulation in atopic dermatitis

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 184, P. 117926 - 117926

Published: Feb. 18, 2025

Language: Английский

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Research Progress on the Efficacy of Immune Checkpoint Inhibitor Combination Therapy in Advanced Non-Small Cell Lung Cancer

Hans Journal of Biomedicine, Journal Year: 2025, Volume and Issue: 15(02), P. 265 - 272

Published: Jan. 1, 2025

Language: Английский

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DECIPHERING THE IMMUNE LANDSCAPE OF OVARIAN CANCER: AN IN-DEPTH ANALYSIS OF IGCH CD4+, CD8+, AND PD-L1 IN TUMOR MICROENVIRONMENT AND THEIR THERAPEUTIC IMPLICATIONS

Medical science of Uzbekistan, Journal Year: 2025, Volume and Issue: 1, P. 22 - 26

Published: Feb. 25, 2025

Relevance. Ovarian cancer is one of the most lethal gynecological malignancies worldwide, with high mortality primarily due to late-stage diagnosis and lack effective early screening. The tumor microenvironment (TME) plays a crucial role in progression, immune evasion, resistance therapy. Immune cells, particularly CD4+ CD8+ T along checkpoint proteins like PD-L1, significantly influence behavior therapeutic response. Understanding their roles ovarian may provide insights into novel immunotherapeutic strategies. Materials methods study. A total 135 patients from Republican Specialized Scientific Practical Medical Center Oncology Radiology, Samarkand Branch, were included this Tumor samples obtained through biopsy or surgical resection, profiling was performed using multiplex immunohistochemistry flow cytometry. expression levels CD4+, CD8+, PD-L1 quantified, spatial distribution within TME analyzed. Correlations between profiles clinical outcomes, including survival rates response immunotherapy, assessed. Research results. helper cells exhibited functional diversity, Th1 promoting anti-tumor immunity, whereas Th2 regulatory (Tregs) contributed suppression advanced tumors. High T-cell infiltration correlated improved survival; however, elevated associated exhaustion (PD-1, TIM-3, LAG-3) evasion. Increased linked poor prognosis, reinforcing its as key regulator. Conclusion. This study highlights prognostic significance cancer. aid personalized treatment strategies, optimizing immunotherapy efficacy. Future research should focus on integrating multi-omics approaches enhance patient stratification improve outcomes.

Language: Английский

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Immunosenescence in autoimmune diseases

Autoimmunity Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 103805 - 103805

Published: March 1, 2025

Language: Английский

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Causal Characteristics of Immune Cells Associated with Aortic Dissection: A Mendelian Randomisation Analysis

European Cardiology Review, Journal Year: 2025, Volume and Issue: 20

Published: April 1, 2025

Background: This study investigates the causal relationships between 731 immune cell traits and aortic dissection (AD) using Mendelian randomisation (MR). By identifying specific phenotypes contributing to AD, we explore their clinical implications for risk stratification therapeutic interventions. Methods: A bivariate MR framework analysed dynamics attributes genetic variants as instrumental variables. Summary statistics from a genome-wide association were obtained. Univariable analysis was conducted inverse-variance weighted method supplemented by sensitivity analyses. Horizontal pleiotropy assessed MR-Egger residual sum outlier. Significant cis-expression quantitative trait loci (eQTL) identified via Genotype-Tissue Expression (GTEx) database, followed tissue-specific expression pathway Results: Four immunophenotypes exhibited positive effects on while one showed negative effect. Pathogenic included median fluorescence intensity of CD19 transitional B cells, immunoglobulin D- CD38dim CD3 CD39+ CD4+ Treg activated cells. The protective absolute count CD86+ myeloid dendritic Sensitivity analyses validated these associations. Pathway enrichment highlighted significant arterial enrichments key biological processes, SLAMF6 CD28 genes. Conclusion: suggests potential roles in AD pathogenesis, although findings should be interpreted with caution due limitations. types associated eQTL genes offer promising targets Future research focus translating into practical strategies patient care.

Language: Английский

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Ultrasound-Energized OX40L-Expressing Biohybrid for Multidimensional Mobilization of Sustained T Cell-Mediated Antitumor Immunity and Potent Sono-Immunotherapy

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Harnessing immunostimulation to reinvigorate antitumor effector immune cells represents a promising strategy for tumor eradication. However, achieving durable clinical outcomes necessitates multidimensional activation sustain robust responses. Here, we present an ultrasound-empowered living biohybrid that strategically mobilizes T-cell-mediated immunity potent sono-immunotherapy. Through synthetic biology, engineer bacteria express fusion protein encoding the costimulatory OX40 ligand (OX40L), and further functionalize them with high-performance polymer sonosensitizer tethered via reactive oxygen species-cleavable linker. Upon ultrasound irradiation, sono-activated nanocargoes detach from bacterial surface, facilitating cellular entry exposing immune-stimulating OX40L. The sonodynamic effects, coupled native immunogenicity of bacteria, promotes tumor-associated antigen release, fosters proinflammatory microenvironment, drives dendritic cell maturation, thereby priming cytotoxic T-cell activation. OX40L expressed by engineered amplifies sustains activity, orchestrating response. This cascade-amplified effectively suppresses growth, induces long-lasting memory, provides protection against metastasis recurrence, significantly enhancing survival outcomes. By integrating ultrasound-energized nanoadjuvants boosters, this hybrid biotherapeutic platform offers versatile powerful activation, advancing frontier cancer

Language: Английский

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Peripheral T-cell subset activation in NMDAR encephalitis: Insights into pathogenesis and biomarker potential for disease monitoring

Clinical Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 110506 - 110506

Published: April 1, 2025

Language: Английский

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The pathogenesis of neurological immune-related adverse events following immune checkpoint inhibitor therapy

Seminars in Immunology, Journal Year: 2025, Volume and Issue: 78, P. 101956 - 101956

Published: April 27, 2025

Cancer is a leading cause of morbidity and mortality worldwide. The development immune checkpoint inhibitors (ICI) has revolutionised cancer therapy, patients who were previously incurable can now have excellent responses. These therapies work by blocking inhibitory pathways, like cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death-1 (PD-1), its ligand PD-L1, lymphocyte activation gene 3 (LAG-3); which leads to increased anti-tumour However, their use lead the immune-related adverse events (irAEs), may result in severe disability, interruption even death. Neurological autoimmune sequelae occur 1-10 % treated with ICIs be fatal. They encompass broad spectrum diseases, affect central peripheral nervous system, include syndromes encephalitis, cerebellitis, neuropathy, myositis. In some cases, neurological irAEs associated autoantibodies recognising neuronal or glial targets. this review, we first describe key targets ICI followed formulation clinical presentations, where focus on syndromes. We comprehensively formulate current literature evaluating surface intracellular autoantibodies, cytokines, chemokines, leukocyte patterns, other blood derived biomarkers, immunogenetic profiles; highlight impact our understanding pathogenesis irAEs. Finally, therapeutic pathways patient outcomes, provide an overview future aspects therapy.

Language: Английский

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