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Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
Published on: August 1, 2025
Reprogramming of TLR-Ferroptosis Signaling and Immunometabolic Pathways Overcomes Myeloid Suppression to Improve
Nabil A Siddiqui1, Li Zhang1, Gabriel DeLeon1
1Department of Radiology, Weill Cornell Medicine, New York, New York.
Cancer Research
|June 15, 2026
Summary
New particle therapy reprograms the Toll-like receptor (TLR)-ferroptosis axis to overcome immune suppression in advanced prostate cancer (PCa). This approach enhances CD8+ T cell infiltration and shows promise for treating refractory malignancies.
Area of Science:
- Oncology
- Immunology
- Nanomedicine
Background:
- Advanced prostate cancer (PCa) exhibits limited immunotherapy response due to immune suppression, stromal remodeling, and metabolic barriers.
- The tumor microenvironment in PCa actively hinders effective antitumor immunity.
Purpose of the Study:
- To characterize the immunometabolic properties of a novel PSMA-targeting silica particle therapy.
- To investigate the strategy of reprogramming the Toll-like receptor (TLR)-ferroptosis axis in Myc-driven PCa.
Main Methods:
- Utilized ultrasmall PSMA-targeting silica particles as a first-in-class therapy.
- Assessed the impact of particles on lipid biosynthesis, ferroptosis induction, and nutrient flux.
- Evaluated the combination therapy with CSF-1R inhibition and immune checkpoint blockade in Myc-overexpressing models.
Main Results:
- Single-agent particles suppressed lipid/steroid biosynthesis and impaired nutrient flux, sensitizing tumors to ferroptosis.
- Therapy induced redox remodeling, stromal reprogramming, and innate immune activation, reversing myeloid suppression.
- Combination therapy suppressed tumor growth, extended survival, and achieved complete remissions in preclinical models.
Conclusions:
- Reprogramming the TLR-ferroptosis axis is a viable strategy for particle-driven immunotherapies in PCa.
- This approach holds significant translational potential for treating immunologically refractory cancers.
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