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Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression.

Research paper by Halime H Kalkavan, Piyush P Sharma, Stefan S Kasper, Iris I Helfrich, Aleksandra A AA Pandyra, Asmae A Gassa, Isabel I Virchow, Lukas L Flatz, Tim T Brandenburg, Sukumar S Namineni, Mathias M Heikenwalder, Bastian B Höchst, Percy A PA Knolle, Guido G Wollmann, Dorothee D von Laer, et al.

Indexed on: 02 Mar '17Published on: 02 Mar '17Published in: Nature communications



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.