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Ascic E, Åkerström F, Sreekumar Nair M, Rosa A, Kurochkin I, Zimmermannova O, Catena X, Rotankova N, Veser C, Rudnik M, Ballocci T, Schärer T, Huang X, de Rosa Torres M, Renaud E, Velasco Santiago M, Met Ö, Askmyr D, Lindstedt M, Greiff L, Ligeon LA, Agarkova I, Svane IM, Pires CF, Rosa FF, Pereira CF
Science 386 (6719) eadn9083 [2024-10-18; online 2024-10-18]
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.
Clinical Genomics Lund [Service]
PubMed 39236156
DOI 10.1126/science.adn9083
Crossref 10.1126/science.adn9083