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Reovirus activates human dendritic cells to promote innate antitumor immunity

Fiona Errington1, Lynette Steele, Robin Prestwich

  • 1Cancer Research U.K., St. James's University Hospital, Beckett Street, Leeds.

Journal of Immunology (Baltimore, Md. : 1950)
|April 22, 2008
PubMed

Insights

Reovirus activates human dendritic cells (DC), stimulating immune responses against cancer. Activated DCs enhance natural killer (NK) and T cell activity, suggesting a new way oncolytic viruses fight tumors.

Area of Science:

  • Immunology
  • Virology
  • Oncology

Background:

  • Oncolytic viruses combat cancer through direct cell lysis and immune system activation.
  • Reovirus is under clinical investigation for cancer treatment, but its immune effects are unclear.
  • Dendritic cells (DCs) are crucial for initiating innate and adaptive immune responses.

Purpose of the Study:

  • To investigate reovirus's ability to activate human dendritic cells (DCs).
  • To determine if reovirus-activated DCs can stimulate other immune cells like NK and T cells.
  • To explore the potential role of DCs in reovirus-mediated antitumor immunity.

Main Methods:

  • Human DCs were exposed to reovirus.
  • DC maturation and cytokine production (IFN-alpha, TNF-alpha, IL-12p70, IL-6) were measured.
  • Reovirus-activated DCs were co-cultured with autologous NK cells and T cells to assess immune cell activation and cytotoxic activity.

Main Results:

  • Reovirus induced DC maturation and pro-inflammatory cytokine production.
  • DC activation was independent of viral replication but influenced by PKR and NF-kappaB signaling.
  • Reovirus-activated DCs enhanced NK cell IFN-gamma production and cytolytic activity.
  • Activated DCs also boosted T cell cytokine secretion (IL-2, IFN-gamma) and induced non-antigen-specific tumor cell killing.

Conclusions:

  • Reovirus directly activates human DCs, stimulating both innate and adaptive immune responses.
  • Reovirus-activated DCs enhance the cytotoxic activity of NK cells and T cells.
  • This DC-mediated immune activation presents a novel mechanism for oncolytic virus therapy, potentially improving reovirus efficacy against cancer.

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