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In vivo dendritic cell reprogramming for cancer immunotherapy

Ascic, Ervin LU orcid ; Åkerström, Fritiof LU ; Sreekumar Nair, Malavika LU ; Rosa, André LU ; Kurochkin, Ilia LU ; Zimmermannova, Olga LU ; Catena, Xavier LU ; Rotankova, Nadezhda ; Veser, Charlotte and Rudnik, Michal , et al. (2024) In Science (New York, N.Y.)
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Science (New York, N.Y.)
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • pmid:39236156
ISSN
1095-9203
DOI
10.1126/science.adn9083
language
English
LU publication?
yes
id
b39505f3-51c8-4fd7-989f-afa1d4689d97
date added to LUP
2024-09-12 10:09:47
date last changed
2024-09-12 13:12:54
@article{b39505f3-51c8-4fd7-989f-afa1d4689d97,
  abstract     = {{<p>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.</p>}},
  author       = {{Ascic, Ervin and Åkerström, Fritiof and Sreekumar Nair, Malavika and Rosa, André and Kurochkin, Ilia and Zimmermannova, Olga and Catena, Xavier and Rotankova, Nadezhda and Veser, Charlotte and Rudnik, Michal and Ballocci, Tommaso and Schärer, Tiffany and Huang, Xiaoli and de Rosa Torres, Maria and Renaud, Emilie and Velasco Santiago, Marta and Met, Özcan and Askmyr, David and Lindstedt, Malin and Greiff, Lennart and Ligeon, Laure-Anne and Agarkova, Irina and Svane, Inge Marie and Pires, Cristiana F and Rosa, Fábio F and Pereira, Carlos-Filipe}},
  issn         = {{1095-9203}},
  language     = {{eng}},
  month        = {{09}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science (New York, N.Y.)}},
  title        = {{In vivo dendritic cell reprogramming for cancer immunotherapy}},
  url          = {{http://dx.doi.org/10.1126/science.adn9083}},
  doi          = {{10.1126/science.adn9083}},
  year         = {{2024}},
}