Truncated CD200 stimulates tumor immunity leading to fewer lung metastases in a novel Wistar rat metastasis model
Truncated CD200 stimulates tumor immunity leading to fewer lung metastases in a novel Wistar rat metastasis model
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DOI：
10.1016/j.bbrc.2018.01.065
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发表时间：
2018-02-05
影响因子：
3.1
通讯作者：
Tanaka, Junya
中科院分区：
文献类型：
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作者：
Kuwabara, Jun;Umakoshi, Akihiro;Tanaka, Junya
CD 200在表达其受体CD 200 R的免疫细胞中介导免疫抑制。有两种CD 200变体;缺少CD 200 R结合所必需的N端序列部分的截短的CD 200（CD 200 S）和全长CD 200（CD 200 L）。我们建立了一种新的肺转移模型，通过皮下移植C6胶质瘤细胞到新生Wistar大鼠背部。所有移植的大鼠都发生了大的背部肿瘤，其中近90%发生了肺转移。为了比较CD 200 S和CD 200 L对肿瘤免疫的作用，类似地移植表达CD 200 L（C6-L）或CD 200 S（C6-S）的C6细胞。结果显示，100%的C6-L肿瘤大鼠发生肺转移，而仅44%的C6-S肿瘤大鼠发生转移（n = 25）。移植后180 d，约20%的C6-S荷瘤大鼠肿瘤消失，避免死亡，而C6-L荷瘤大鼠45 d后全部死亡。下一代测序显示，C6-S肿瘤表达的趋化因子和颗粒酶B的水平比C6-L肿瘤高得多。流式细胞术显示C6-S肿瘤含有更多的死亡细胞和更多的CD 45（+）细胞，包括自然杀伤细胞和CD 8（+）淋巴细胞。特别是，表达CD 11 c、MHC II类、CD 8和/或CD 103的树突状细胞的多个亚群在C6-S中比在C6-L肿瘤中更丰富。这些结果表明，CD 200 S诱导了多个树突状细胞亚群的积累，这些树突状细胞亚群激活了细胞毒性T淋巴细胞，从而消除了转移性肿瘤细胞。(C)2018爱思唯尔公司All rights reserved.
CD200 mediates immunosuppression in immune cells that express its receptor, CD200R. There are two CD200 variants; truncated CD200 that lacks the part of N-terminal sequence necessary for CD200R binding (CD200S) and full-length CD200 (CD200L). We established a novel lung metastasis model by subcutaneously transplanting C6 glioma cells into the backs of neonatal Wistar rats. All transplanted rats developed large back tumors, nearly 90% of which bore lung metastases. To compare the effects of CD200S and CD200L on tumor immunity, CD200L (C6-L)- or CD200S (C6-S)-expressing C6 cells were similarly transplanted. The results showed that 100% of rats with C6-L tumors developed lung metastases, while metastases were found in only 44% of rats with C6-S tumors (n = 25). Tumors disappeared in approximately 20% of the C6-S-bearing rats, and these animals evaded death 180 d after transplantation, while all C6-L tumor-bearing rats died after 45 d. Next generation sequencing revealed that C6-S tumors expressed chemokines and granzyme B at much higher levels than C6-L tumors. Flow cytometry revealed that C6-S tumors contained more dead cells and more CD45(+) cells, including natural killer cells and CD8(+) lymphocytes. In particular, multiple subsets of dendritic cells expressing CD11c, MHC class II, CD8, and/or CD103 were more abundant in C6-S than in C6-L tumors. These results suggested that CD200S induced the accumulation of multiple dendritic cell subsets that activated cytotoxic T lymphocytes, leading to the elimination of metastasizing tumor cells. (C) 2018 Elsevier Inc. All rights reserved.