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Metal-Phenolic Nanomedicines Targeting Fatty Acid Metabolic Reprogramming to Overcome Immunosuppression in Radiometabolic Cancer Therapy.
ACS Appl Mater Interfaces
January 2025
Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
Radiation therapy (RT) is a prevalent cancer treatment; however, its therapeutic outcomes are frequently impeded by tumor radioresistance, largely attributed to metabolic reprogramming characterized by increased fatty acid uptake and oxidation. To overcome this limitation, we developed polyphenol-metal coordination polymer (PPWQ), a novel nanoradiotherapy sensitizer specifically designed to regulate fatty acid metabolism and improve RT efficacy. These nanoparticles (NPs) utilize a metal-phenolic network (MPN) to integrate tungsten ions (W), quercetin (QR), and a PD-L1-blocking peptide within a PEG-polyphenol scaffold.
View Article and Find Full Text PDFBackground: For patients with head and neck squamous cell carcinoma (HNSCC), failure of definitive radiation combined with cisplatin nearly universally results in death. Although hyperactivation of the Nrf2 pathway can drive radiation and cisplatin resistance along with suppressed anti-tumor immunity, treatment-refractory HNSCC tumors may retain sensitivity to targeted agents secondary to synergistic lethality with other oncogenic drivers (e.g.
View Article and Find Full Text PDFSystemic IFN-I combined with topical TLR7/8 agonists promotes distant tumor suppression by c-Jun-dependent IL-12 expression in dendritic cells.
Nat Cancer
January 2025
Center for Cancer Research, Medical University of Vienna, Comprehensive Cancer Center, Vienna, Austria.
Dendritic cell (DC) activation by pattern recognition receptors like Toll-like-receptors (TLRs) is crucial for cancer immunotherapies. Here, we demonstrate the effectiveness of the TLR7/8 agonist imiquimod (IMQ) in treating both local tumors and distant metastases. Administered orally, IMQ activates plasmacytoid DCs (pDCs) to produce systemic type I interferons (IFN-I) required for TLR7/8 upregulation in DCs and macrophages, sensitizing them to topical IMQ treatment, which is essential for therapeutic efficacy.
View Article and Find Full Text PDFEngineered allogeneic stem cells orchestrate T lymphocyte driven immunotherapy in immunosuppressive leptomeningeal brain metastasis.
J Natl Cancer Inst
January 2025
Center for Stem Cell and Translational Immunotherapy, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA.
Background: Immune-checkpoint inhibitors have shown clinical benefit in non-small cell lung cancer (NSCLC) derived brain metastasis (BM), however, their efficacy in lung to leptomeningeal brain metastasis (LLBM) remains poor.
Methods: A paired matched RNA expression dataset of patients with NSCLCs and BMs was analyzed to idenfiy BM specific suppressive tumor microenvironment (TME) features. Next, we created immune-competent LLBM mouse models that mimic clinical LLBM.
IL-35 modulates Tfh2 and Tfr cell balance to alleviate allergic rhinitis.
Inflamm Res
January 2025
Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
Background: Allergic rhinitis (AR) represents a persistent inflammatory condition affecting the upper respiratory tract, characterized by abnormal initiation of the immunoglobulin E (IgE)-mediated cascade. Follicular helper T (Tfh) cells and regulatory T (Tfr) cells are pivotal in orchestrating the development of IgE production in AR patients. IL-35, an anti-inflammatory cytokine, secreted by various cellular subpopulations.
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