title: Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression.
abstract: Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. New therapeutic approaches that induce a strong and prolonged immune activation would represent a major immunotherapeutic advance. Here we show that the arenaviruses lymphocytic choriomeningitis virus (LCMV) and the clinically used Junin virus vaccine (Candid#1) preferentially replicate in tumour cells in a variety of murine and human cancer models. Viral replication leads to prolonged local immune activation, rapid regression of localized and metastatic cancers, and long-term disease control. Mechanistically, LCMV induces antitumour immunity, which depends on the recruitment of interferon-producing Ly6C+monocytes and additionally enhances tumour-specific CD8+T cells. In comparison with other clinically evaluated oncolytic viruses and to PD-1 blockade, LCMV treatment shows promising antitumoural benefits. In conclusion, therapeutically administered arenavirus replicates in cancer cells and induces tumour regression by enhancing local immune responses.
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany.|Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Halime
authors.identifier: 0000-0002-0090-4080
authors.initials: H
authors.lastname: Kalkavan
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Piyush
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kasper
authors.affiliation: Department of Dermatology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Helfrich
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Aleksandra A
authors.initials: AA
authors.lastname: Pandyra
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany.|Department of Cardiothoracic Surgery, Cologne University Heart Center, Kerpener Strasse 62, 50937 Cologne, Germany.
authors.forename: Asmae
authors.initials: A
authors.lastname: Gassa
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Virchow
authors.affiliation: Department of Dermatology/Allergology, Cantonal Hospital, Rorschacher Strasse 95, St. Gallen 9007, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Flatz
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Brandenburg
authors.affiliation: Department of Virology, Technical University of Munich, Schneckenburgstrasse 8, 81675 Munich, Germany.
authors.forename: Sukumar
authors.initials: S
authors.lastname: Namineni
authors.affiliation: Department of Virology, Technical University of Munich, Schneckenburgstrasse 8, 81675 Munich, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.affiliation: Institute of Molecular Immunology/Experimental Oncology, München Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Höchst
authors.affiliation: Institute of Molecular Immunology/Experimental Oncology, München Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany.
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
authors.affiliation: Division for Virology, Medical University Innsbruck, Peter-Mayr-Strasse 4b, 6020 Innsbruck, Austria.
authors.forename: Guido
authors.initials: G
authors.lastname: Wollmann
authors.affiliation: Division for Virology, Medical University Innsbruck, Peter-Mayr-Strasse 4b, 6020 Innsbruck, Austria.
authors.forename: Dorothee
authors.initials: D
authors.lastname: von Laer
authors.affiliation: Institute of Virology, Düsseldorf University Hospital, Heinrich Heine University, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Drexler
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, 90033 California, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Rathbun
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, 90033 California, USA.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Cannon
authors.affiliation: Institute of Medical Microbiology and Hospital Hygiene, University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Stefanie
authors.identifier: 0000-0002-9707-8191
authors.initials: S
authors.lastname: Scheu
authors.affiliation: Institute of Medical Microbiology and Hospital Hygiene, University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Bauer
authors.affiliation: Ludwig Institute for Cancer Research, University of Oxford, Old Road Campus, Research Building, Old Road Campus, Headington, Oxford OX3 7DQ, UK.
authors.forename: Jagat
authors.initials: J
authors.lastname: Chauhan
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.affiliation: Institute of Immunology (Charité - University Medicine Berlin), 3125 Berlin, Germany.|German Cancer Research Center (DKFZ), 13125 Heidelberg, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Willimsky
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin and German Rheumatism Research Center (DRFZ), Charitéplatz 1, D-10117 Berlin, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Löhning
authors.affiliation: Department of Dermatology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.|German Cancer Consortium (DKTK), Partner Site University Hospital Essen, 45122 Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Department of Otorhinolaryngology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.|German Cancer Consortium (DKTK), Partner Site University Hospital Essen, 45122 Essen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schuler
authors.affiliation: Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.affiliation: Institute of Immunology, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
mesh_terms: D000818:Animals; D018050:Arenavirus / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D007157:Immunologic Surveillance; D007370:Interferon Type I / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000821:virology*; D050504:Oncolytic Viruses / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: D007370:Interferon Type I; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor