Investigational New Drugs, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 27, 2024
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Окт. 18, 2024
Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.
Язык: Английский
Процитировано
39
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Янв. 2, 2025
Suppression of chimeric antigen receptor-modified T (CAR-T) cells by the immunosuppressive tumor microenvironment remains a major barrier to their efficacy against solid tumors. To address this, we develop an anti-PD-L1-expressing nanovesicle loaded with STING agonist cGAMP (aPD-L1 NVs@cGAMP) remodel and thereby enhance CAR-T cell activity. Following pulmonary delivery, nanovesicles rapidly accumulate in lung selectively deliver agonists PD-L1-overexpressing via PD-1/PD-L1 interaction. This targeted delivery effectively avoids systemic inflammation poor cellular uptake that plague free agonists. Internalized trigger signaling induce interferon responses, which diminish populations such as myeloid-derived suppressor promote infiltration. Importantly, anti-PD-L1 single chain variable fragment on surface blocks PD-L1 upregulation induced prevents exhaustion. In both orthotopic cancer metastasis model, combined therapy aPD-L1 NVs@cGAMP potently inhibits growth recurrence. Therefore, is expected serve effective enhancer improve The hindered Here authors report design characterization inhalable cGAMP, showing enhanced activity models.
Язык: Английский
Процитировано
3
Discover Oncology, Год журнала: 2025, Номер 16(1)
Опубликована: Фев. 5, 2025
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers, characterized by high morbidity and mortality rates. Recently, immunotherapy has emerged as a crucial treatment modality for HCC, following surgery, locoregional therapies, targeted therapies. This approach harnesses body's immune system to target eliminate cancer cells, potentially resulting in durable antitumor responses. However, acquired resistance tumor immunosuppressive microenvironment (TIME) significantly hinder its clinical application. advancements nanotechnology, coupled with deeper understanding biology nano-biological interactions, have led development various nanoparticles aimed at enhancing therapeutic efficacy through specific targeting tissues. These increase accumulation immunotherapeutic drugs within microenvironment, thereby transforming TIME. In this review, we provide concise overview fundamental principles governing TIME landscape HCC discuss rationale applications context. Additionally, highlight existing challenges potential opportunities translation nanomedicines.
Язык: Английский
Процитировано
0
Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер unknown, С. 104654 - 104654
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер 209, С. 104658 - 104658
Опубликована: Фев. 15, 2025
Язык: Английский
Процитировано
0
CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(3)
Опубликована: Март 1, 2025
Neuroinflammation caused by excessive activation of microglia is a significant cause poor prognosis in ischemic stroke patients. Minocycline, microglial cell inhibitor, has neuroprotective effects stroke, but its optimal treatment duration and specific mechanisms action remain unclear. This study aimed to compare the efficacy different minocycline durations on explore their action. We investigated various polarization using cellular animal models. The long-term therapy for were explored through vitro vivo experiments. In models, showed stronger inhibitory effect neuroinflammation improved neuron viability compared with short-term treatment. Further results indicated that downregulated glycolysis levels EMB/MCT4 axis, promoting transformation an anti-inflammatory phenotype inhibiting STING pathway, thereby improving post-stroke neuroinflammation. Long-term exerts regulating EMB/MCT4/STING axis inflammatory downregulating levels. Extending appropriately may further improve outcomes.
Язык: Английский
Процитировано
0
Vaccines, Год журнала: 2025, Номер 13(4), С. 371 - 371
Опубликована: Март 31, 2025
Low antigen immunogenicity poses a significant challenge in vaccine development, often leading to inadequate immune responses and reduced efficacy. Therefore, the discovery of potent immune-enhancing adjuvants is crucial. STING (stimulator interferon genes) agonists are promising class which have been identified various cells activated response DNA fragments, triggering broad range type-I interferon-dependent responses. Integrating with components an ideal strategy bolster vaccine-induced immunity infections cancer cells. Several currently under investigation preclinical studies clinical trials; however, some shown limited efficacy, while others exhibit off-target effects. To ensure safety, they typically delivered carriers that high biocompatibility insolubility. In this review, we present latest research on natural synthetic effectively used summarize their application adjuvant preventive therapeutic vaccines. Additionally, discuss safety as by reviewing potential delivery strategies. Overall, incorporating into formulations represents advancement significantly enhance improve However, ongoing still required identify most effective safe strategies for agonists, well evaluate long-term efficacy trials.
Язык: Английский
Процитировано
0
iScience, Год журнала: 2025, Номер unknown, С. 112324 - 112324
Опубликована: Март 1, 2025
Detecting cytoplasmic or extracellular DNA from host pathogen origin by sensor cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggers immune responses with secretion type I interferons inflammatory cytokines. However, STING agonists function as type-2 adjuvant promoting allergic asthma. Here, we asked how cGAS/STING signaling pathway influences allergen-induced in models airway diseases induced birch pollen extract, house dust mite, ovalbumin plus Alum. We report increased dsDNA the airways, together cGAS gene expression, following allergen challenge these models, correlating cytokine IL-4, IL-5, IL-13 release. Allergen-induced were reduced cGAS- STING-deficient mice. Further, blocking specific inhibitor RU.521 protected mice inflammation responses. Thus, sensing contributes to may represent a therapeutic target for lung inflammation.
Язык: Английский
Процитировано
0
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(9), С. 4025 - 4025
Опубликована: Апрель 24, 2025
As an evolutionarily conserved and ubiquitous mechanism of host defense, non-immune cells in vertebrates possess the intrinsic ability to autonomously detect combat intracellular pathogens. This process, termed cell-autonomous immunity, is distinct from classical innate immunity. In this review, we comprehensively examine defense mechanisms employed by response pathogen invasion. We provide a detailed analysis cytosolic sensors that recognize aberrant nucleic acids, lipopolysaccharide (LPS), other pathogen-associated molecular patterns (PAMPs). Specifically, elucidate underlying key signaling pathways, including cyclic GMP-AMP synthase (cGAS)-stimulator interferon genes (STING) pathway, retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mitochondrial antiviral (MAVS) axis, guanylate-binding proteins (GBPs)-mediated pathway. Furthermore, critically evaluate involvement these pathways pathogenesis various diseases, autoimmune disorders, inflammatory conditions, malignancies, while highlighting their potential as therapeutic targets.
Язык: Английский
Процитировано
0
Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13
Опубликована: Апрель 28, 2025
Tumor metabolism plays a pivotal role in shaping immune responses within the tumor microenvironment influencing progression, evasion, and efficacy of cancer therapies. Radiotherapy has been shown to impact both modulation, often inducing activation through damage-associated molecular patterns STING pathway. In this study, we analyse particular characteristics tumour metabolic its effect on microenvironment. We also review changes that are induced by radiotherapy, with focus sensitisation effects radiotherapy. Our aim is contribute development research ideas field radiotherapy metabolic-immunological studies.
Язык: Английский
Процитировано
0