EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes.
EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes.
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DOI：
10.1038/oncsis.2014.40
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发表时间：
2014-11-03
期刊：
影响因子：
6.2
通讯作者：
Inoue, S.
中科院分区：
文献类型：
--
作者：
Miyazaki, T.;Ikeda, K.;Horie-Inoue, K.;Kondo, T.;Takahashi, S.;Inoue, S.
雌激素受体结合片段相关抗原9(EBAG9)是我们先前利用CpG基因组结合位点克隆技术在MCF-7乳腺癌细胞中发现的一个主要的雌激素反应基因。EBAG9蛋白在恶性肿瘤中表达上调，提示该蛋白参与了肿瘤的病理生理过程。在本研究中，我们研究了EBAG9在Ebag9基因敲除(Ebag9KO)小鼠体内对移植瘤的宿主防御中的作用。将MB-49小鼠膀胱癌细胞接种于Ebag9KO小鼠皮下，并设对照组。我们发现，与对照组相比，Ebag9KO小鼠MB-49细胞的肿瘤形成和肺转移显著减少。与对照组相比，Ebag9KO组小鼠肿瘤组织中CD8+、CD3+和CD4+T细胞的浸润增加。值得注意的是，从Ebag9KO小鼠肿瘤中分离的CD8+T细胞与对照组小鼠肿瘤中的CD8+T细胞相比，显示出免疫和化学吸引相关基因的显著上调，包括白细胞介素10受体、干扰素伽马、颗粒酶A、颗粒酶B和趋化因子受体3。从Ebag9KO小鼠肿瘤中分离的CD8+T细胞也表现出增强的脱颗粒和增强的细胞溶解活性。此外，在Ebag9KO宿主体内过继转移从肿瘤中分离的CD8+T细胞可以抑制野生型宿主MB-49细胞的生长。这些结果表明，EBAG9通过负性调节宿主防御中的获得性免疫反应来调节肿瘤的生长和转移。EBAG9可能成为肿瘤免疫治疗的潜在靶点。
Estrogen receptor-binding fragment-associated antigen 9 (EBAG9) is a primary estrogen-responsive gene that we previously identified in MCF-7 breast cancer cells using the CpG genomic binding-site cloning technique. The expression of EBAG9 protein is often upregulated in malignant tumors, suggesting that this protein is involved in cancer pathophysiology. In the present study, we investigated the role of EBAG9 in host defense against implanted tumors in Ebag9-knockout (Ebag9KO) mice. MB-49 mouse bladder cancer cells were subcutaneously implanted into Ebag9KO and control mice. We found that tumor formation and metastasis to the lung by MB-49 cells were substantially reduced in Ebag9KO mice compared with control mice. The infiltration of CD8+, CD3+ and CD4+ T cells into the generated tumors was enhanced in Ebag9KO mice compared with controls. Notably, CD8+ T cells isolated from tumors in Ebag9KO mice exhibited substantial upregulation of immunity- and chemoattraction-related genes, including interleukin-10 receptor, interferon gamma, granzyme A, granzyme B and chemokine (C-X-C motif) receptor 3 compared with CD8+ T cells from tumors in control mice. The CD8+ T cells isolated from tumors in Ebag9KO mice also exhibited enhanced degranulation and increased cytolytic activity. Furthermore, the adoptive transfer of CD8+ T cells isolated from tumors in Ebag9KO host could repress tumor growth by MB-49 cells implanted in wild-type host. These results suggest that EBAG9 modulates tumor growth and metastasis by negatively regulating the adaptive immune response in host defense. EBAG9 could be a potential target for tumor immunotherapy.
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影响因子：
11.2
作者：
Harlin H;Meng Y;Peterson AC;Zha Y;Tretiakova M;Slingluff C;McKee M;Gajewski TF
通讯作者：
Gajewski TF
细胞毒性T淋巴细胞颗粒是分泌的溶酶体，含有穿孔蛋白和颗粒酶。
DOI：
10.1084/jem.173.5.1099
发表时间：
1991-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Peters PJ;Borst J;Oorschot V;Fukuda M;Krähenbühl O;Tschopp J;Slot JW;Geuze HJ
通讯作者：
Geuze HJ
DOI：
10.1084/jem.184.3.963
发表时间：
1996-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Loetscher M;Gerber B;Loetscher P;Jones SA;Piali L;Clark-Lewis I;Baggiolini M;Moser B
通讯作者：
Moser B
影响因子：
4.2
作者：
Gerard, CM;Bruyns, C;Velu, T
通讯作者：
Velu, T
DOI：
10.1084/jem.187.12.2009
发表时间：
1998-06-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cole KE;Strick CA;Paradis TJ;Ogborne KT;Loetscher M;Gladue RP;Lin W;Boyd JG;Moser B;Wood DE;Sahagan BG;Neote K
通讯作者：
Neote K