Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Language: Английский
Advanced Materials, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 16, 2025
The radiotherapy-induced release of DNA fragments can stimulate the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator interferon genes (cGAS-STING) pathway to prime antitumor immunity, but this is expected be less potent because inefficient cytosolic delivery negatively charged fragments. In study, manganese-coordinated chitosan (CS-Mn) microparticles with selective DNA-capturing capacity are concisely prepared via a coordination-directed one-pot synthesis process potentiate immunogenicity radiotherapy. obtained CS-Mn that undergo rapid disassembly under physiological conditions selectively bind form positively DNA-CS assemblies strong electrostatic interaction between linear and molecules. They thus enable efficient in presence serum cooperate Mn2+ activate cGAS-STING dendritic cells. Upon intratumoral injection, markedly enhance efficacy radiotherapy against both irradiated distal tumors different tumor models collectively promoting tumor-infiltrating CD8+ T-cell stemness activation innate immunity. radiosensitization effect further augmented by concurrently applying anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. This work highlights an ingenious strategy prepare Trojan horse-like as cGAS-STING-activating radiosensitizers for effective radioimmunotherapy.
Language: Английский
Citations
2
Science Immunology, Journal Year: 2025, Volume and Issue: 10(103)
Published: Jan. 17, 2025
Immune responses against cancer are dominated by T cell exhaustion and dysfunction. Recent advances have underscored the critical role of early priming interactions in establishing fates. In this review, we explore importance dendritic (DC) signals specifying CD8+ fates cancer, drawing on insights from acute chronic viral infection models. We highlight DCs lymph nodes tumors maintaining stem-like cells, which for durable antitumor immune responses. Understanding how determined will enable rational design immunotherapies, particularly therapeutic vaccines, that can modulate DC-T to generate beneficial
Language: Английский
Citations
1
Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)
Published: Jan. 23, 2025
Abstract Background Acute rejection (AR) is one of the significant factors contributing to poor prognosis in patients following kidney transplantation. Neutrophils are main cause early host-induced tissue injury. This paper intends investigate possible mechanisms neutrophil involvement acute renal Methods Samples were analyzed for their relationship with immune cells using CIBERSORT. WGCNA was used identify modules high relevance neutrophils and hub genes extracted. The effect on function after blocking formyl peptide receptor 1 (FPR1) tested vitro experiments. effects FPR1 as well vivo constructing a mouse transplant model. Results proportion higher AR group than non-rejection group, identified an important gene regulation transplantation by neutrophils. At cellular level, inhibited activation ERK1/2 pathway, decreased ferrous ion content, affected expression iron metabolism-related proteins, suppressed formation NETs. In model transplantation, blockade graft infiltration NETs content. Meanwhile, attenuated injury during rejection. Conclusion study found that might be molecule involved explored between neutrophils, provided potential treatment methods clinical practice.
Language: Английский
Citations
1
Cell, Journal Year: 2025, Volume and Issue: unknown
Published: March 1, 2025
Language: Английский
Citations
1
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
Citations
4
Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 19, 2025
Abstract Membrane protein degradation techniques hijacking lysosome targeting receptors (LTRs) have provided new opportunities to develop anticancer therapeutics. However, due varied expression of these LTRs and potential influence on their native biological function resulting from excessive endocytosis, developing alternative membrane degraders is highly desirable. Here, Ferritac (ferritin‐based chimeras) developed, a plug‐and‐play platform that displayed multivalent antibodies via Spycatcher‐Spytag chemistry crosslink the ectodomains nearby for degradation. Based receptor crosslinking, obviates dependence specific LTRs. This study reveals nanoparticles efficiently degraded epidermal growth factor (EGFR) both in vitro vivo. In mechanistic studies, Ferritac‐Anti‐EGFR adopted clathrin‐based endocytosis mainly involved with pathways degradation, which are successfully expanded degrade PD‐L1 (programmed death‐ligand 1) HER2 (human 2) vitro. Moreover, efficient by Ferritac‐Anti‐PD‐L1 induce potent immune response vivo validated MC38 B16F10 tumor models. Further combined chemotherapeutics paclitaxel, saw satisfactory synergistic therapeutic effect. Overall, could be easily applied various targets directly attaching relevant promising candidate as novel versatile LTR‐independent degrader.
Language: Английский
Citations
0
Neoplasia, Journal Year: 2025, Volume and Issue: 64, P. 101155 - 101155
Published: March 31, 2025
Language: Английский
Citations
0
Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)
Published: Feb. 14, 2025
Abstract One-carbon metabolism (1CM) has been reported to promote cancer progression across various malignancies. While 1CM is critical for cell proliferation by enhancing nucleotide synthesis, its physiological roles within different types in the tumor immune microenvironment (TIME) still remain unclear. In this study, we analyzed bulk-RNA sequencing and single-cell RNA (scRNA-seq) data from lung adenocarcinoma (LUAD) patients elucidate functional of TIME. Moreover, examined scRNA-seq treated with immunotherapy cancers, including LUAD, glioblastoma, renal carcinoma, colorectal cancer, triple-negative breast cancer. Compared other types, gene profiles are significantly enriched a specific subset T cells. Intriguingly, these high-1CM cells identified as proliferative intermediate exhausted (Tex int ). Furthermore, Tex received most robust CD137 signaling. Consistently, analysis LUAD undergoing anti-PD1 demonstrated that exhibited higher scores increased This observation was particularly pronounced non-responders immunotherapy, where population expanded. We further established prominent signaling pathway resistant multiple types. Collectively, identify distinctive who do not respond immunotherapy. These findings propose targeting may represent novel therapeutic strategy enhance efficacy mitigating diverse cancers.
Language: Английский
Citations
0
Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Language: Английский
Citations
0