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

Nat Commun. 2017 Mar 1;8:14447. doi: 10.1038/ncomms14447.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arenavirus / physiology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Humans
  • Immunologic Surveillance*
  • Interferon Type I / metabolism*
  • Lymphocyte Activation / immunology
  • Lymphocytic choriomeningitis virus / physiology
  • Mice, Inbred C57BL
  • Monocytes / metabolism
  • Neoplasms / blood supply
  • Neoplasms / immunology*
  • Neoplasms / virology*
  • Oncolytic Viruses / metabolism
  • Programmed Cell Death 1 Receptor / metabolism
  • Virus Replication / physiology*

Substances

  • Interferon Type I
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor