Restoring tumor immunogenicity with dendritic cell reprogramming

Article Article scientifique Article Restoring tumor immunogenicity with dendritic cell reprogramming eng 2023-07-14 author Zimmermannova Olga 0000-0002-5706-8124 Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. author Ferreira Alexandra G. 0000-0001-8918-1183 Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. author Ascic Ervin 0000-0002-3839-0572 Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. author Velasco Santiago Marta 0000-0002-3322-3513 National Center of Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark. author Kurochkin Ilia 0000-0003-3100-0903 Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. author Hansen Morten 0000-0002-3738-3100 National Center of Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark. author Met Özcan 0000-0002-3256-7592 National Center of Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark. author Caiado Inês 0000-0001-5015-2705 Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. author Shapiro Ilja E. Ludwig Institute for Cancer Research, Lausanne Branch—University of Lausanne (UNIL), Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. author Michaux Justine Ludwig Institute for Cancer Research, Lausanne Branch—University of Lausanne (UNIL), Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. author Humbert Marion 0000-0002-1710-1479 Department of Pathology and Immunology, Geneva Medical School, Av. de Champel 41, 1206 Geneva, Switzerland. 726517 author Soto-Cabrera Diego 0000-0001-8023-0006 Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. author Benonisson Hreinn 0000-0002-2974-2038 Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. author Silvério-Alves Rita Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. author Gomez-Jimenez David 0000-0002-9375-5263 Department of Immunotechnology, Lund University, Medicon Village, Scheelevägen 2, 223 81 Lund, Sweden. author Bernardo Carina 0000-0002-1667-6510 Division of Oncology, Department of Clinical Sciences, Lund, Medicon Village, Scheelevägen 2, 223 81 Lund, Sweden. author Bauden Monika 0000-0001-6088-9268 Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital, 221 85 Lund, Sweden. author Andersson Roland 0000-0003-0778-8630 Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital, 221 85 Lund, Sweden. author Höglund Mattias Division of Oncology, Department of Clinical Sciences, Lund, Medicon Village, Scheelevägen 2, 223 81 Lund, Sweden. author Miharada Kenichi 0000-0001-8073-4001 Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. author Nakamura Yukio 0000-0001-6834-4123 Cell Engineering Division, RIKEN BioResource Research Center, 3-1-1 Koyadai, 305-0074, Tsukuba, Ibaraki, Japan. author Hugues Stéphanie 0000-0002-1031-5909 Department of Pathology and Immunology, Geneva Medical School, Av. de Champel 41, 1206 Geneva, Switzerland. 663452 Département de pathologie et immunologie (PATIM) author Greiff Lennart 0000-0002-7004-1989 Department of ORL, Head and Neck Surgery, Skåne University Hospital, 221 85 Lund, Sweden. author Lindstedt Malin 0000-0001-9136-1087 Department of Immunotechnology, Lund University, Medicon Village, Scheelevägen 2, 223 81 Lund, Sweden. author Rosa Fábio F. 0000-0002-7714-5852 Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. author Pires Cristiana F. 0000-0003-2985-6323 Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. author Bassani-Sternberg Michal 0000-0002-1934-954X Ludwig Institute for Cancer Research, Lausanne Branch—University of Lausanne (UNIL), Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. author Svane Inge Marie 0000-0002-9451-6037 National Center of Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark. author Pereira Carlos-Filipe 0000-0002-9724-1382 Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden. eadd4817 10.1126/sciimmunol.add4817 37418548 2470-9468 PMC7614848 https://www.science.org/doi/10.1126/sciimmunol.add4817 Decreased antigen presentation contributes to the ability of cancer cells to evade the immune system. We used the minimal gene regulatory network of type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen-presenting cells (tumor-APCs). Enforced expression of the transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient to induce the cDC1 phenotype in 36 cell lines derived from human and mouse hematological and solid tumors. Within 9 days of reprogramming, tumor-APCs acquired transcriptional and epigenetic programs associated with cDC1 cells. Reprogramming restored the expression of antigen presentation complexes and costimulatory molecules on the surfaces of tumor cells, allowing the presentation of endogenous tumor antigens on MHC-I and facilitating targeted killing by CD8 + T cells. Functionally, tumor-APCs engulfed and processed proteins and dead cells, secreted inflammatory cytokines, and cross-presented antigens to naïve CD8 + T cells. Human primary tumor cells could also be reprogrammed to increase their capability to present antigen and to activate patient-specific tumor-infiltrating lymphocytes. In addition to acquiring improved antigen presentation, tumor-APCs had impaired tumorigenicity in vitro and in vivo. Injection of in vitro generated melanoma-derived tumor-APCs into subcutaneous melanoma tumors delayed tumor growth and increased survival in mice. Antitumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors. Our approach serves as a platform for the development of immunotherapies that endow cancer cells with the capability to process and present endogenous tumor antigens. Dewey 616.07 European Research Council 866448 137 Département de pathologie et immunologie 21F false 563 Pathologie et immunologie 906 Science immunology 8 85 6066eada-b7bc-4fde-81b3-861d53d1e1d2 Article (Accepted version) Public 2023_Zimmermannova_ScImmunol.pdf 4524544 application/pdf 0f7c34ad7701dda6e15154d7d61d98e123f63aeb432c1085d35daeb5dd291c77 openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Restoring tumor immunogenicity with dendritic cell reprogramming	Science immunology			2023	302	1,360

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Humbert, Marion