The peripheral immune status of granulocytic myeloid-derived suppressor cells correlates the survival in advanced gastric cancer patients receiving cisplatin-based chemotherapy
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Hirokazu Shoji1,2, Kohei Tada3, Shigehisa Kitano4, Takashi Nishimura1, Yasuhiro Shimada1, Kengo Nagashima5, Kazunori Aoki6, Nobuyoshi Hiraoka7, Yoshitaka Honma1, Satoru Iwasa1, Atsuo Takashima1, Ken Kato1, Narikazu Boku1, Kazufumi Honda8, Tesshi Yamada2,8, Yuji Heike3 and Tetsuya Hamaguchi1
1Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan
2Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
3Immunotherapy and Cell Therapy Service, St. Lucas International Hospital, Tokyo, Japan
4Exploratory Oncology Research and Clinical Trial Center, Division of Cancer Immunotherapy, National Cancer Center, Tokyo, Japan
5Department of Global Clinical Research, Graduate School of Medicine, Chiba University, Chiba, Japan
6Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
7Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan
8Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, Japan
Yuji Heike, email: [email protected]
Keywords: gastric cancer, peripheral immune status, granulocytic myeloid-derived suppressor cells, chemotherapy, prognosis
Received: October 22, 2016 Accepted: April 24, 2017 Published: May 30, 2017
Background: The prognostic significance of peripheral immune status in patients with advanced gastric cancer (AGC) remains unclear.
Results: From July 2013 through December 2014, 37 patients were enrolled. Among patients with 25 subsets of immune cells, patients in the high group of granulocytic myeloid-derived suppressor cells (Gr-MDSCs) showed significantly shorter progression-free survival (PFS) than those in the low group (3.98 vs. 8.78 months; hazards ratio (HR), 2.61; p = 0.01). In multivariate analysis, the high Gr-MDSCs value was also associated with shorter PFS (HR, 4.60; 95% confidence interval (CI), 1.79−11.8; p = 0.001). Although significant difference was not found in univariate analysis, the high Gr-MDSCs group was associated with shorter overall survival (OS) (HR, 2.89; 95% CI, 1.23–6.80; p = 0.015) in multivariate analysis.
Materials and Methods: In this explorative prospective study, peripheral blood samples were collected from AGC patients before initiating first-line cisplatin-based chemotherapy (S-1 + cisplatin or S-1 + cisplatin + docetaxel). Peripheral blood mononuclear cells were analyzed for 25 immune subsets by multicolor flow cytometry. PFS and OS were compared between the patients divided into high and low (≥ and < median, respectively) groups based on the median value for each immune cell subset.
Conclusions: The peripheral immune status of Gr-MDSCs appears to affect the prognosis in AGC. Further research is needed to confirm the clinical value of the level of circulating Gr-MDSCs as a prognostic and/or predictive marker in AGC.
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