Takashima Ken, Takeda Yohei, Oshiumi Hiroyuki, Shime Hiroaki, Okabe Masaru, Ikawa Masahito, Matsumoto Misako, Seya Tsukasa
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka, 565-0871, Japan.
Biochem Biophys Res Commun. 2016 Sep 30;478(4):1764-71. doi: 10.1016/j.bbrc.2016.09.021. Epub 2016 Sep 5.
An interferon-inducing DNA sensor STING participates in tumor rejection in mouse models. Here we examined what mechanisms contribute to STING-dependent growth retardation of B16 melanoma sublines by NK cells in vivo. The studies were designed using WT and STING KO black mice, and B16D8 (an NK-sensitive melanoma line having STING) and STING KO B16D8 sublines established for this study. The results from tumor-implant studies suggested that STING in host immune cells and tumor cells induced distinct profiles of chemokines including CXCL10, CCL5 and IL-33, and both participated in NK cell infiltration and activation in B16D8 tumor. Spontaneous activation of STING occurs in host-immune and tumor cells of this NK-sensitive tumor, thereby B16D8 tumor growth being suppressed in this model. Our data show that STING induces tumor cytotoxicity by NK cells through tumor and host immune cell network to contribute to innate surveillance and suppression of tumors in vivo.
一种干扰素诱导性DNA传感器——干扰素基因刺激蛋白（STING）参与小鼠模型中的肿瘤排斥反应。在此，我们研究了在体内NK细胞介导的B16黑色素瘤亚系依赖STING的生长迟缓的机制。本研究使用野生型（WT）和STING基因敲除（KO）的黑色小鼠，以及为本研究建立的B16D8（一种具有STING的NK敏感黑色素瘤细胞系）和STING KO B16D8亚系。肿瘤植入研究结果表明，宿主免疫细胞和肿瘤细胞中的STING诱导了包括CXCL10、CCL5和IL-33在内的不同趋化因子谱，二者均参与了B16D8肿瘤中的NK细胞浸润和激活。在这种NK敏感肿瘤的宿主免疫细胞和肿瘤细胞中发生了STING的自发激活，从而在该模型中抑制了B16D8肿瘤的生长。我们的数据表明，STING通过肿瘤和宿主免疫细胞网络诱导NK细胞产生肿瘤细胞毒性，从而有助于体内对肿瘤的天然监测和抑制。
