Restoring tumor immunogenicity with dendritic cell reprogramming.

Autor:	Zimmermannova O; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden., Ferreira AG; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden.; CNC-Centre for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês do Pombal, 3004-517 Coimbra, Portugal.; Doctoral Programme in Experimental Biology and Biomedicine, University of Coimbra, Largo Marquês do Pombal, 3004-517 Coimbra, Portugal., Ascic E; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden., Velasco Santiago M; National Center of Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark., Kurochkin I; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden., Hansen M; National Center of Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark., Met Ö; National Center of Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark.; Department of Health Technology, Technical University of Denmark, Ørsteds Pl. 345C, 2800 Kongens Lyngby, Denmark., Caiado I; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden.; CNC-Centre for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês do Pombal, 3004-517 Coimbra, Portugal.; Doctoral Programme in Experimental Biology and Biomedicine, University of Coimbra, Largo Marquês do Pombal, 3004-517 Coimbra, Portugal., Shapiro IE; Ludwig Institute for Cancer Research, Lausanne Branch-University of Lausanne (UNIL), Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.; Department of Oncology-University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Rue du Bugnon 46, CH-1011 Lausanne, Switzerland., Michaux J; Ludwig Institute for Cancer Research, Lausanne Branch-University of Lausanne (UNIL), Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.; Department of Oncology-University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Rue du Bugnon 46, CH-1011 Lausanne, Switzerland., Humbert M; Department of Pathology and Immunology, Geneva Medical School, Av. de Champel 41, 1206 Geneva, Switzerland.; Center for Infectious Medicine, Huddinge Hospital, Karolinska Institutet, Alfred Nobels Allé 8, 141 52 Huddinge, Sweden., Soto-Cabrera D; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden., Benonisson H; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden., Silvério-Alves R; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden.; CNC-Centre for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês do Pombal, 3004-517 Coimbra, Portugal.; Doctoral Programme in Experimental Biology and Biomedicine, University of Coimbra, Largo Marquês do Pombal, 3004-517 Coimbra, Portugal., Gomez-Jimenez D; Department of Immunotechnology, Lund University, Medicon Village, Scheelevägen 2, 223 81 Lund, Sweden., Bernardo C; Division of Oncology, Department of Clinical Sciences, Lund, Medicon Village, Scheelevägen 2, 223 81 Lund, Sweden., Bauden M; Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital, 221 85 Lund, Sweden., Andersson R; Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital, 221 85 Lund, Sweden., Höglund M; Division of Oncology, Department of Clinical Sciences, Lund, Medicon Village, Scheelevägen 2, 223 81 Lund, Sweden., Miharada K; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; International Research Center for Medical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo-Ku, Kumamoto 860-0811, Japan., Nakamura Y; Cell Engineering Division, RIKEN BioResource Research Center, 3-1-1 Koyadai, 305-0074, Tsukuba, Ibaraki, Japan., Hugues S; Department of Pathology and Immunology, Geneva Medical School, Av. de Champel 41, 1206 Geneva, Switzerland., Greiff L; Department of ORL, Head and Neck Surgery, Skåne University Hospital, 221 85 Lund, Sweden.; Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden., Lindstedt M; Department of Immunotechnology, Lund University, Medicon Village, Scheelevägen 2, 223 81 Lund, Sweden., Rosa FF; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden.; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden., Pires CF; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden.; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden., Bassani-Sternberg M; Ludwig Institute for Cancer Research, Lausanne Branch-University of Lausanne (UNIL), Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.; Department of Oncology-University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Rue du Bugnon 46, CH-1011 Lausanne, Switzerland., Svane IM; National Center of Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark., Pereira CF; Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, BMC A12, 221 84 Lund, Sweden.; Wallenberg Center for Molecular Medicine at Lund University, BMC A12, 221 84 Lund, Sweden.; CNC-Centre for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês do Pombal, 3004-517 Coimbra, Portugal.; Asgard Therapeutics AB, Medicon Village, 223 81 Lund, Sweden.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2023 Jul 14; Vol. 8 (85), pp. eadd4817. Date of Electronic Publication: 2023 Jul 07.
DOI:	10.1126/sciimmunol.add4817
Abstrakt:	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.
Databáze:	MEDLINE
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