TY - JOUR
T1 - In vivo dendritic cell reprogramming for cancer immunotherapy
AU - Ascic, Ervin
AU - Åkerström, Fritiof
AU - Nair, Malavika Sreekumar
AU - Rosa, André
AU - Kurochkin, Ilia
AU - Zimmermannova, Olga
AU - Catena, Xavier
AU - Rotankova, Nadezhda
AU - Veser, Charlotte
AU - Rudnik, Michal
AU - Ballocci, Tommaso
AU - Schärer, Tiffany
AU - Huang, Xiaoli
AU - de Rosa Torres, Maria
AU - Renaud, Emilie
AU - Santiago, Marta Velasco
AU - Met, Özcan
AU - Askmyr, David
AU - Lindstedt, Malin
AU - Greiff, Lennart
AU - Ligeon, Laure Anne
AU - Agarkova, Irina
AU - Svane, Inge Marie
AU - Pires, Cristiana F.
AU - Rosa, Fábio F.
AU - Pereira, Carlos Filipe
N1 - Publisher Copyright:
© 2024 the authors,
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.1126/science.adn9083
DO - 10.1126/science.adn9083
M3 - Journal article
C2 - 39236156
AN - SCOPUS:85206133102
SN - 2096-5672
VL - 386
JO - Journal of Bio-X Research
JF - Journal of Bio-X Research
IS - 6719
M1 - eadn9083
ER -