Enhanced Tumor Immunotherapy by Triple Amplification Effects of Nanomedicine on the STING Signaling Pathway in Dendritic Cells DOI
Xiangyu Wang, Yi Yan, Xia Guo

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Abstract Insufficient activation of stimulator interferon genes (STING) signaling pathway in tumor‐associated dendritic cells limits the efficiency tumor immunotherapy. Herein, “three‐in‐one” IAHA‐LaP/siPTPN6 NPs containing lanthanum ions (La 3+ ), cGAMP, and PTPN6 siRNA are developed for triple amplification STING pathway. In vitro results demonstrate that La significantly promotes cGAMP‐mediated by enhancing phosphorylation STING, TBK1, IRF3, NF‐ κ B p65. Moreover, further enhance p65 augment K63‐linked ubiquitination protein via siPTPN6‐mediated downregulation SHP‐1 protein. Furthermore, improve secretion IFN β (2.4‐fold), IL‐6 (1.5‐fold), TNF‐ α (1.4‐fold), thereby promoting DCs maturation compared to mixture cGAMP. vivo show remarkably inhibit primary growth increasing percentage mature tumor‐draining lymph nodes, polarizing M2/M1 phenotype TME, infiltration CD8 + T into tumors. these dramatically prevent distal inducing systemic anti‐tumor immunity generating a long‐term memory protection against recurrence mice bearing bilateral B16F10. These may offer promising platform robust immune responses.

Language: Английский

Cold and hot tumors: from molecular mechanisms to targeted therapy DOI Creative Commons
Bo Wu, Bo Zhang, Bowen Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 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.

Language: Английский

Citations

68
Inhalable nanovesicles loaded with a STING agonist enhance CAR-T cell activity against solid tumors in the lung DOI Creative Commons
Tianchuan Zhu, Yuchen Xiao, Zhenxing Chen

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 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.

Language: Английский

Citations

7
The Role of cGAS-STING in Remodeling the Tumor Immune Microenvironment Induced by Radiotherapy DOI
Qingyu Jiang,

Zhiheng Chen,

Jin Jiang

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: 209, P. 104658 - 104658

Published: Feb. 15, 2025

Language: Английский

Citations

2
Harnessing nanoparticles for reshaping tumor immune microenvironment of hepatocellular carcinoma DOI Creative Commons
Jinsong Li,

GuanBo Zhang,

Gang Li

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 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.

Language: Английский

Citations

1
Unraveling the link between cholesterol and immune system in cancer: from biological mechanistic insights to clinical evidence. A narrative review DOI
Federica Pecci, Valeria Cognigni, Giulia Claire Giudice

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: unknown, P. 104654 - 104654

Published: Feb. 1, 2025

Language: Английский

Citations

1
Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in mice. DOI Creative Commons

Pauline Chenuet,

Manon Mellier,

Yasmine Messaoud-Nacer

et al.

iScience, Journal Year: 2025, Volume and Issue: unknown, P. 112324 - 112324

Published: March 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.

Language: Английский

Citations

1
Recent advancements in cGAS-STING activation, tumor immune evasion, and therapeutic implications DOI
Md Saiful Islam, Mohammad Saiful Islam, Mst Rubaiat Nazneen Akhand

et al.

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(11)

Published: Oct. 18, 2024

Language: Английский

Citations

4
cGAS-STING DNA-sensing in inflammatory bowel diseases DOI

Georges Dimitrov,

Bernhard Ryffel, Dieudonnée Togbe

et al.

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

3
Long‐Term Minocycline Treatment Exhibits Enhanced Therapeutic Effects on Ischemic Stroke by Suppressing Inflammatory Phenotype of Microglia Through the EMB/MCT4/STING Pathway DOI Creative Commons

Cheng Bo,

Sifeng Liu, Ling Gao

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(3)

Published: March 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.

Language: Английский

Citations

0
Progress Update on STING Agonists as Vaccine Adjuvants DOI Creative Commons

Yanru Shen,

Weijin Huang, Jianhui Nie

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 371 - 371

Published: March 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.

Language: Английский

Citations

0