Tomoro Hishiki1,2,3, Naoko Mise4,5, Kazuaki Harada4,5, Fumie Ihara5, Mariko Takami5, Takeshi Saito4, Keita Terui4, Mitsuyuki Nakata4, Shugo Komatsu4, Hideo Yoshida4, Shinichiro Motohashi5. 1. Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. hishiki-tmr@umin.ac.jp. 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. hishiki-tmr@umin.ac.jp. 3. Division of Pediatric Surgical Oncology, National Cancer Center Hospital, Tokyo, Japan. hishiki-tmr@umin.ac.jp. 4. Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. 5. Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
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.
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 cancerpatients, the numbers of circulating iNKT cells were not decreased in pediatric cancerpatients. α-GalCer stimulation induced a proliferative response in all of the patients.
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