Hiroki Izumi1, Akira Yamasaki2, Kenichi Takeda3, Masahiro Kodani4, Hirokazu Touge5, Natsumi Tanaka6, Masaaki Yanai7, Yasuto Ueda8, Tomohiro Sakamoto9, Shizuka Nishii-Ito10, Haruhiko Makino11, Kosuke Yamaguchi12, Tadashi Igishi13, Eiji Shimizu14. 1. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: hiroizu0211@gmail.com. 2. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: yamasaki@med.tottori-u.ac.jp. 3. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: takedake@med.tottori-u.ac.jp. 4. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: kodani@med.tottori-u.ac.jp. 5. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: touge-hirokazu@yoagomc.jp. 6. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: n.tanaka@med.tottori-u.ac.jp. 7. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: yanai@med.tottori-u.ac.jp. 8. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: uedaya@pref.tottori.jp. 9. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: t-sakamoto@med.tottori-u.ac.jp. 10. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: sito@med.tottori-u.ac.jp. 11. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: hmakino@med.tottori-u.ac.jp. 12. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: kske2@med.tottori-u.ac.jp. 13. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: igishi@med.tottori-u.ac.jp. 14. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. Electronic address: eiji@med.tottori-u.ac.jp.
Abstract
OBJECTIVES: Zoledronate (ZOL) is usually used for prevention of skeletal-related events in cancer patients with bone metastases. The first administration of ZOL is occasionally associated with development of acute-phase reaction (APR), which is due to activation of γδ T cells. ZOL-related APR was associated with better overall survival (OS) of patients with non-small cell lung cancer (NSCLC) in our previous retrospective study. However, it remains to be clarified whether γδ T cells are more activated in patients who experienced ZOL-related APR, and whether γδ T cell activation is involved in prolongation of OS. MATERIALS AND METHODS: Twenty-three patients with advanced NSCLC were recruited between 2012 and 2014 in this study. We administered ZOL to participants with standard care. The patient characteristics, change in γδ T cell counts and cytokines, OS, and skeletal-related event-free survival were compared between patients with APR (APR group) and those without APR (non-APR group). RESULTS: Ten patients (43.5%) experienced a ZOL-related APR. The number of γδ T cells at baseline in the APR group was significantly higher than that in the non-APR group. Serum interleukin-6 and tumor necrosis factor-α in the APR group were significantly increased, but no change in the number of γδ T cells was observed after the first administration of ZOL in both groups. OS in the APR group was significantly longer than that in the non-APR group (median survival time: 23.1 vs. 14.5 months, p < 0.01). CONCLUSION: We showed that APR is related to higher numbers of γδ T cells at baseline and increased cytokines after the first ZOL administration, but not to proliferative responses of γδ T cells. In addition, better OS was observed in the APR group. Therefore, the number of γδ T cells might be a prognostic marker in patients with NSCLC.
OBJECTIVES:Zoledronate (ZOL) is usually used for prevention of skeletal-related events in cancerpatients with bone metastases. The first administration of ZOL is occasionally associated with development of acute-phase reaction (APR), which is due to activation of γδ T cells. ZOL-related APR was associated with better overall survival (OS) of patients with non-small cell lung cancer (NSCLC) in our previous retrospective study. However, it remains to be clarified whether γδ T cells are more activated in patients who experienced ZOL-related APR, and whether γδ T cell activation is involved in prolongation of OS. MATERIALS AND METHODS: Twenty-three patients with advanced NSCLC were recruited between 2012 and 2014 in this study. We administered ZOL to participants with standard care. The patient characteristics, change in γδ T cell counts and cytokines, OS, and skeletal-related event-free survival were compared between patients with APR (APR group) and those without APR (non-APR group). RESULTS: Ten patients (43.5%) experienced a ZOL-related APR. The number of γδ T cells at baseline in the APR group was significantly higher than that in the non-APR group. Serum interleukin-6 and tumor necrosis factor-α in the APR group were significantly increased, but no change in the number of γδ T cells was observed after the first administration of ZOL in both groups. OS in the APR group was significantly longer than that in the non-APR group (median survival time: 23.1 vs. 14.5 months, p < 0.01). CONCLUSION: We showed that APR is related to higher numbers of γδ T cells at baseline and increased cytokines after the first ZOL administration, but not to proliferative responses of γδ T cells. In addition, better OS was observed in the APR group. Therefore, the number of γδ T cells might be a prognostic marker in patients with NSCLC.