International Immunopharmacology, Journal Year: 2025, Volume and Issue: 154, P. 114505 - 114505
Published: March 31, 2025
Language: Английский
Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)
Published: Feb. 7, 2025
Glioblastoma multiforme (GBM) is the most common and aggressive primary intracranial malignancy. It characterized by insufficient infiltration of anti-tumor T lymphocytes within tumor microenvironment (TME), rendering it an "immune cold" disease. This immune deficiency results in poor responses to checkpoint blockade (ICB) therapies. Recent studies have demonstrated that bacteria can proliferate tumors activate responses. Therefore, this study, we employed Escherichia coli (E. coli) combination with anti-PD-1 antibodies treat GBM, aim exploring immune-activating potential E. GBM its synergistic effect on therapy. The antibody therapy were administered intravenously intraperitoneally, respectively. Complete blood cell count, biochemical analysis, hematoxylin eosin (H&E) staining, agar plate culture evaluate biosafety tumor-targeting capability coli. ELISA kits used detect innate cytokines. Flow cytometry immunofluorescence staining investigate cells. Tumor volume tumor-bearing mice was recorded combined treatment efficacy. H&E observe inhibition markers. E.coli specifically target into region, response mice. Immunofluorescence flow group exhibited a significant upregulation cytotoxic CD8+ cells marked suppression regulatory compared control group. expression Ki67 significantly downregulated, TUNEL revealed increased number apoptotic Furthermore, growth rate slower than exhibits activity further regulate tissues synergize providing new insights enhance efficacy immunotherapy.
Language: Английский
Citations
0
Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(788)
Published: March 5, 2025
Radiotherapy (RT) has been the standard-of-care treatment for patients with glioblastoma (GBM); however, clinical effectiveness is hindered by therapeutic resistance. Here, we demonstrated that tumor immune microenvironment (TIME) exhibited immunosuppressive properties and high expression of Golgi phosphoprotein 3 like (GOLPH3L) in RT-resistant GBM. Our study showed GOLPH3L interacted stimulator interferon genes (STING) at aspartic acid residue 184 after RT, leading to coat protein complex II-mediated retrograde transport STING from endoplasmic reticulum. This suppressed STING-NOD-like receptor thermal domain associated (NLRP3)-mediated pyroptosis, resulting suppressive TIME, driving GBM resistance RT. Genetic ablation cells augmented antitumor immunity overcame Moreover, have identified a small molecular inhibitor GOLPH3L, vitamin B5 calcium (VB5), which improved efficacy RT checkpoint blockade inducing robust response mouse models. Clinically, treated VB5 responses Thus, reprogramming TIME targeting may offer potential opportunity improve
Language: Английский
Citations
0
Aging and Disease, Journal Year: 2025, Volume and Issue: unknown, P. 0 - 0
Published: Jan. 1, 2025
The aging immune system presents profound challenges, notably through the decline of T cell function, which is critical for effective responses. As age-related changes lead to diminished diversity and heighten immunosuppressive environments, older individuals face increased susceptibility infections, autoimmune diseases, reduced efficacy immunotherapies. This review investigates intricate mechanisms by drives immunosenescence, including suppression, evasion, antigen reactivity, overexpression checkpoint molecules. By delving into innovative therapeutic strategies aimed at rejuvenating populations modifying immunological landscape, we highlight potential enhancing resilience in elderly. Ultimately, our goal outline actionable pathways restoring thereby improving health outcomes facing decline.
Language: Английский
Citations
0
OncoImmunology, Journal Year: 2025, Volume and Issue: 14(1)
Published: March 24, 2025
Renal cell carcinoma (RCC) is recognized as an immunogenic tumor, yet tumor-infiltrating lymphocytes often exhibit diminished effector function. However, the mechanisms underlying reduced T and NK activity in RCC remain unclear. Here, we examined immune contexture patients undergoing nephrectomy to identify immune-related biomarkers associated with disease progression. Immune phenotypes secretion profiles were assessed using flow cytometry Luminex multiplex analysis. Supervised multivariate analysis revealed several changes of which frequencies cells expressing CCR5, CXCR3, PD-1 elevated within tumors compared peripheral blood. In addition, higher levels regulatory cells, PD-1+, CXCR3+ observed relapse following nephrectomy. With regards soluble factors, tumor-derived CXCL8 was Fuhrman grade increased frequency polymorphonuclear myeloid-derived suppressor (PMN-MDSCs). These demonstrate potential relevance progression merit further investigation prospective studies.
Language: Английский
Citations
0
International Immunopharmacology, Journal Year: 2025, Volume and Issue: 154, P. 114505 - 114505
Published: March 31, 2025
Language: Английский
Citations
0