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Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells.
Ervin Ascic1, Gaia Fontanari1, Maria Thrasyvoulou1
1Molecular Medicine and Gene Therapy, Science for Life Laboratory, Lund Stem Cell Centre, Lund University; Wallenberg Centre for Molecular Medicine, Lund University.
Researchers developed a new cancer immunotherapy by reprogramming tumor cells into dendritic cells (cDC1-like cells) within the tumor microenvironment. This approach enhances anti-tumor immunity by boosting cytotoxic T cell responses against solid tumors.
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Area of Science:
- Immunology
- Cancer Biology
- Biotechnology
Background:
- Type 1 conventional dendritic cells (cDC1s) are crucial for anti-cancer T cell responses.
- Current methods for generating cDC1s for immunotherapy are limited by low yield, functional variability, and tumor microenvironment (TME) suppression.
Purpose of the Study:
- To develop a novel in vivo reprogramming strategy to convert cancer cells into cDC1-like cells within the TME.
- To establish a tractable protocol for generating immunogenic cDC1-like cells for enhanced cancer immunotherapy.
Main Methods:
- Overexpression of the core cDC1 gene network (PU.1, IRF8, BATF3 - PIB) in cancer cells.
- Subcutaneous implantation of a mixture of PIB-transduced and parental cancer cells.
- Monitoring of cell surface markers (CD45, MHC class II) as readouts for reprogramming efficiency.
Main Results:
- In vivo reprogramming in the YUMM1.7 melanoma model showed faster kinetics and higher efficiency than in vitro methods.
- Reprogrammed cDC1-like cells induced rapid TME remodeling, immune cell infiltration, and tertiary lymphoid structure formation within 9 days.
- Reprogrammed cells persisted in tumors for at least 9 days, demonstrating sustained immunogenic potential.
Conclusions:
- The described in vivo cDC1 reprogramming protocol offers a robust method to convert "immune-cold" tumors into "immune-hot" tumors.
- This approach provides a platform for studying cDC1-mediated anti-tumor immunity and exploring combination immunotherapies.

