Sequential actions of immune effector cells induced by viral activation of dendritic cells to eliminate murine neuroblastoma

J Pediatr Surg. 2018 Aug;53(8):1615-1620. doi: 10.1016/j.jpedsurg.2017.08.019. Epub 2017 Aug 26.


Purpose: In preclinical trails, we reported the antitumor effect of dendritic cells activated with Sendai virus (rSeV/DC) combined with γ-irradiation against neuroblastoma. However, what kind of effector cells for the combined therapy were used to show the antitumor effect was unclear. In this study, we performed radiation and rSeV/DC therapy in vivo and examined the effector cells involved.

Methods: Dendritic cells were cultured from bone marrow cells, activated with SeV and administered intratumorally at 106 weekly for 3weeks. Radiation was administered at 4Gy/time × 3 times. During the treatment, CD4+ and CD8+ cells and natural killer (NK) cells were removed by antibodies.

Results: Complete remission of neuroblastoma was observed in 62.5% of individuals in the combined therapy group. By depleting the effector cells using antibodies, the tumor increased in size from an early stage of treatment in the CD4+ and NK cell-depleted group. In contrast, the tumor increased in size in the late stage of treatment in the CD8+ cell-depleted group.

Conclusion: The combination of radiation and rSeV/DC therapy induces different effector cells, depending on the time point during treatment.

Level of evidence: V.

Keywords: Dendritic cell; Irradiation; Neuroblastoma; Recombinant Sendai virus.

MeSH terms

  • Animals
  • Bone Marrow Cells / pathology
  • Dendritic Cells / immunology*
  • Humans
  • Killer Cells, Natural
  • Lymphocyte Activation / immunology*
  • Mice
  • Neuroblastoma / immunology*
  • Neuroblastoma / pathology
  • Sendai virus
  • Virus Activation / immunology*