Restoring tumor immunogenicity with dendritic cell reprogramming

• DOI: 10.1126/sciimmunol.add4817
• Publication Date: 2023-07-07T17:59:09Z
• Authors: Olga Zimmermannova; Alexandra G. Ferr...; Ervin Ascic; Marta Velasco San...; Ilia Kurochkin; Morten Hansen; Özcan Met; Inês Caiado; Ilja E. Shapiro; Justine Michaux; Marion Humbert; Diego Soto-Cabrera; Hreinn Benonisson; Rita Silvério-Alves; David Gomez-Jimenez; Carina Bernardo; Monika Bauden; Roland Andersson; Mattias Höglund; Kenichi Miharada; Yukio Nakamura; Stephanie Hugues; Lennart Greiff; Malin Lindstedt; Fábio F. Rosa; Cristiana F. Pires; Michal Bassani-St...; Inge Marie Svane; Carlos-Filipe Per...
• Keywords: Reprogramming; Follicular dendritic cells

Decreased antigen presentation contributes to the ability of cancer cells evade immune system. We used minimal gene regulatory network type 1 conventional dendritic (cDC1) reprogram into professional antigen-presenting (tumor-APCs). Enforced expression transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient induce cDC1 phenotype in 36 cell lines derived from human mouse hematological solid tumors. Within 9 days reprogramming, tumor-APCs acquired transcriptional epigenetic programs associated with cells. Reprogramming restored complexes costimulatory molecules on surfaces tumor cells, allowing endogenous antigens MHC-I facilitating targeted killing by CD8+ T Functionally, engulfed processed proteins dead secreted inflammatory cytokines, cross-presented naïve Human primary could also be reprogrammed increase their capability present activate patient-specific tumor-infiltrating lymphocytes. In addition acquiring improved presentation, had impaired tumorigenicity vitro vivo. Injection generated melanoma-derived subcutaneous melanoma tumors delayed growth increased survival mice. Antitumor immunity elicited synergistic checkpoint inhibitors. Our approach serves as a platform for development immunotherapies that endow process antigens.