In vivo dendritic cell reprogramming for cancer immunotherapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39236156.
- Also identified by DOI 10.1126/science.adn9083 and PMC identifier 7616765.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells; induced tumor regressions; and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy.
Medical subject headings
- Cellular Reprogramming
- Dendritic Cells
- Immunotherapy
- T-Lymphocytes, Cytotoxic
- Tumor Microenvironment
- Cellular Reprogramming Techniques
- Neoplasms