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Frequency and proliferative response of circulating invariant natural killer T cells in pediatric patients with malignant solid tumors

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Abstract

Background

Invariant natural killer T (iNKT) cells play an important role in tumor immunity, enhancing both innate and acquired immunity. We have previously shown the enhancement of antibody-dependent cellular cytotoxicity against neuroblastoma by activated iNKT cells. As a first step towards clinical application, we studied the frequency and proliferative response of circulating iNKT cells in children with and without cancer.

Methods

Blood samples were collected from 10 patients with pediatric malignant solid tumors and 11 patients with non-neoplastic diseases (control). The frequency of circulating iNKT cells was quantified by flow cytometry. Whole peripheral blood mononuclear cells were then stimulated with α-galactosylceramide (α-GalCer) for 7 days, and the expansion rate of the iNKT-cell fraction was assessed.

Results

The frequency of iNKT cells in the patients of the cancer and control group did not differ to a statistically significant extent. The iNKT-cell population increased after α-GalCer stimulation in all cases. The iNKT cells of patients who had undergone intensive chemotherapy also had the potential to expand in vitro.

Conclusions

Unlike adult cancer patients, the numbers of circulating iNKT cells were not decreased in pediatric cancer patients. α-GalCer stimulation induced a proliferative response in all of the patients.

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Acknowledgements

This work was supported by Grants from the Ministry of Education, Culture, Sports, Science and Technology Grant-in-Aid for Scientific Research (C) Number 235926242.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

    Tomoro Hishiki, Naoko Mise, Kazuaki Harada, Takeshi Saito, Keita Terui, Mitsuyuki Nakata, Shugo Komatsu & Hideo Yoshida

  2. Division of Surgical Oncology, Children’s Cancer Center, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Tomoro Hishiki

  3. Division of Pediatric Surgical Oncology, National Cancer Center Hospital, Tokyo, Japan

    Tomoro Hishiki

  4. Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Naoko Mise, Kazuaki Harada, Fumie Ihara, Mariko Takami & Shinichiro Motohashi

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  1. Tomoro Hishiki
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  2. Naoko Mise
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  3. Kazuaki Harada
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Correspondence to Tomoro Hishiki.

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Conflict of interest

The authors declare no conflicts of interest in association with the present study.

Informed consent

All analyses were performed in accordance with the Declaration of Helsinki and were approved by the institutional review board. Informed consent for the usage of surplus tumor tissue was obtained from the human subjects who participated in this study.

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Hishiki, T., Mise, N., Harada, K. et al. Frequency and proliferative response of circulating invariant natural killer T cells in pediatric patients with malignant solid tumors. Pediatr Surg Int 34, 169–176 (2018). https://doi.org/10.1007/s00383-017-4185-1

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  • DOI: https://doi.org/10.1007/s00383-017-4185-1

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