In vivo dendritic cell reprogramming for cancer immunotherapy

Ervin Ascic, Fritiof Åkerström, Malavika Sreekumar Nair, André Rosa, Ilia Kurochkin, Olga Zimmermannova, Xavier Catena, Nadezhda Rotankova, Charlotte Veser, Michal Rudnik, Tommaso Ballocci, Tiffany Schärer, Xiaoli Huang, Maria de Rosa Torres, Emilie Renaud, Marta Velasco Santiago, Özcan Met, David Askmyr, Malin Lindstedt, Lennart GreiffLaure Anne Ligeon, Irina Agarkova, Inge Marie Svane, Cristiana F. Pires, Fábio F. Rosa, Carlos Filipe Pereira*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
Article numbereadn9083
JournalJournal of Bio-X Research
Volume386
Issue number6719
Number of pages17
ISSN2096-5672
DOIs
Publication statusPublished - 2024

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