期刊
CANCER MEDICINE
卷 5, 期 1, 页码 49-60出版社
WILEY-BLACKWELL
DOI: 10.1002/cam4.550
关键词
Antitumor immunity; autologous hematopoietic stem cell transplantation; homeostatic proliferation; neutrophil; NK cell
类别
资金
- Ministry of Health, Labour and Welfare of Japan
- Practical Research for Innovative Cancer Control
- Japan Agency for Medical Research and Development
- program for promotion of Foundation Studies in Health Science of the National Institute of Biomedical Innovation (NIBIO)
- National Cancer Center Research and Development Fund [23-A-38, 26-A-11, 26-A-12]
Autologous hematopoietic stem cell transplantation (HSCT) can induce a strong antitumor immunity by homeostatic proliferation (HP) of T cells and suppression of regulatory T cells following preconditioning-induced lymphopenia. However, the role of innate immunity including natural killer (NK) cells is still not understood. Here, first, we examined whether NK cells exert an antitumor effect after syngeneic HSCT in a murine colon cancer model. Flow cytometry showed that NK cells as well as T cells rapidly proliferated after HSCT, and the frequency of mature NK cells was increased in tumor during HP. Furthermore, NK cells undergoing HP were highly activated, which contributed to substantial tumor suppression. Then, we found that a large number of neutrophils accumulated in tumor early after syngeneic HSCT. It was recently reported that neutrophil-derived mediators modulate NK cell effector functions, and so we examined whether the neutrophils infiltrated in tumor are associated with NK cell-mediated antitumor effect. The depletion of neutrophils significantly impaired an activation of NK cells in tumor and increased the fraction of proliferative NK cells accompanied by a decrease in NK cell survival. The results suggested that neutrophils in tumor prevent NK cells from activation-induced cell death during HP, thus leading to a significant antitumor effect by NK cells. This study revealed a novel aspect of antitumor immunity induced by HSCT and may contribute to the development of an effective therapeutic strategy for cancer using HSCT.
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