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

J Pediatr Surg

Department of Pediatric Surgery, Reproductive and Developmental Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Published: August 2018

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 10 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.

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http://dx.doi.org/10.1016/j.jpedsurg.2017.08.019DOI Listing

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