In vivo dendritic cell reprogramming for cancer immunotherapy

• 成果类型: Article
• 署名作者: Ascic, Ervin; Akerstrom, Fritiof; Sreekumar Nair, Malavika; Rosa, Andre; Kurochkin, Ilia; Zimmermannova, Olga; Catena, Xavier; Rotankova, Nadezhda; Veser, Charlotte; Rudnik, Michal; Ballocci, Tommaso; Schaerer, Tiffany; Huang, Xiaoli; de Rosa Torres, Maria; Renaud, Emilie; Velasco Santiago, Marta; Met, Ozcan; Askmyr, David; Lindstedt, Malin; Greiff, Lennart; Ligeon, Laure-Anne; Agarkova, Irina; Svane, Inge Marie; Pires, Cristiana F.; Rosa, Fabio F.; Pereira, Carlos-Filipe
• 署名单位: Lund University; Lund University; InSphero AG; University of Copenhagen; Copenhagen University Hospital; Technical University of Denmark; Lund University; Skane University Hospital; Lund University; Lund University; Universidade de Coimbra
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12426
• DOI: 10.1126/science.adn9083
• 发表日期: 2024-10-18
• 关键词: functional-neurons; responses; antigen; fibroblasts; cdc1

摘要

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.