In vivo dendritic cell reprogramming for cancer immunotherapy
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.
Authors
- David Askmyr (ORCID: https://orcid.org/0000-0003-1312-8524)
- Ervin Ascic (ORCID: https://orcid.org/0000-0002-3839-0572)
- Carlos‐Filipe Pereira (ORCID: https://orcid.org/0000-0002-9724-1382)
- M. Nair (ORCID: https://orcid.org/0000-0003-1378-7247)
- Emilie Renaud (ORCID: https://orcid.org/0000-0003-4747-1195)
- Xavier Catena (ORCID: https://orcid.org/0000-0001-7885-2447)
- Nadezhda Rotankova
- Michał Rudnik (ORCID: https://orcid.org/0000-0002-8716-6729)
- Malin Lindstedt (ORCID: https://orcid.org/0000-0001-9136-1087)
- Laure‐Anne Ligeon (ORCID: https://orcid.org/0000-0002-4522-5807)
- Inge Marie Svane (ORCID: https://orcid.org/0000-0002-9451-6037)
- André Rosa (ORCID: https://orcid.org/0000-0002-3179-4160)
- Ilia Kurochkin (ORCID: https://orcid.org/0000-0003-3100-0903)
- Fábio F. Rosa (ORCID: https://orcid.org/0000-0002-7714-5852)
- Lennart Greiff (ORCID: https://orcid.org/0000-0002-7004-1989)
- Özcan Met (ORCID: https://orcid.org/0000-0002-3256-7592)
- Cristiana F. Pires (ORCID: https://orcid.org/0000-0003-2985-6323)
- M. Torres (ORCID: https://orcid.org/0009-0009-0005-7860)
- Fritiof Åkerström (ORCID: https://orcid.org/0009-0005-4071-3771)
- Marta Velasco Santiago (ORCID: https://orcid.org/0000-0002-3322-3513)
- Olga Zimmermannová (ORCID: https://orcid.org/0000-0002-5706-8124)
- Tommaso Ballocci
- Tiffany Schärer (ORCID: https://orcid.org/0009-0007-8008-9939)
- Charlotte Veser
- Xiaoli Huang (ORCID: https://orcid.org/0009-0004-3853-0020)
- Irina Agarkova
Institutions
- Lund University (SE)
- Herlev Hospital (DK)
- Medicon Village (SE)
- Inspire (CH)
- Wallenberg Wood Science Center (SE)
- Skåne University Hospital (SE)
- University of Coimbra (PT)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Science
- Published
- 2024-09-05
- DOI
- https://doi.org/10.1126/science.adn9083
- Citations
- 97
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 23.33
Funders
- Cancer Research Institute
- University of Pennsylvania
- European Commission
- Cancerfonden
- Lunds Universitet
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Science for Life Laboratory
- Novo Nordisk Fonden
- Fundação para a Ciência e a Tecnologia
- Eurostars