Intraepithelial Lymphocytes Suppress Intestinal Tumor Growth by Cell-to-Cell Contact via CD103/E-Cadherin Signal.
Intraepithelial Lymphocytes Suppress Intestinal Tumor Growth by Cell-to-Cell Contact via CD103/E-Cadherin Signal.
复制标题
DOI：
10.1016/j.jcmgh.2021.01.014
复制
发表时间：
2021
影响因子：
7.2
通讯作者：
Okamoto R
中科院分区：
文献类型：
--
作者：
Morikawa R;Nemoto Y;Yonemoto Y;Tanaka S;Takei Y;Oshima S;Nagaishi T;Tsuchiya K;Nozaki K;Mizutani T;Nakamura T;Watanabe M;Okamoto R
小肠癌比结肠直肠癌更罕见的原因尚不清楚。我们假设，上皮内淋巴细胞（IEL），这是丰富的小肠，是最接近的免疫细胞上皮细胞，通过细胞与细胞接触，排除肿瘤细胞。我们开发了DPE-绿色荧光蛋白（DPE-GFP）×腺瘤性结肠息肉病;多发性肠肿瘤（APCmin）小鼠，这是一种自发性肠肿瘤的T细胞报告小鼠。我们可视化IEL在肠道肿瘤微环境中的动力学和IEL与上皮细胞之间的相互作用，以及细胞与细胞接触在抗肠道肿瘤免疫中的作用，使用一种新的体内实时成像系统和一种新的体外共培养系统。在小肠肿瘤微环境中，T细胞在血管周围的运动受到限制，IEL和上皮细胞之间相互作用的频率降低。CD103基因缺失降低了IEL与上皮细胞之间的相互作用频率，并增加了小肠肿瘤的数量。在共培养系统中，野生型IEL扩增并浸润到来自APC min小鼠的肠肿瘤类器官，并降低它们的活力，这是细胞与细胞接触和CD103依赖性的。小肠中IEL的丰富可能有助于肿瘤的低数量，尽管由于IEL的稀疏，该系统可能在结肠中不起作用。增加结肠中IEL数量或增强IEL与上皮细胞之间的细胞与细胞接触的策略可能对预防具有高癌症风险的患者的肠道肿瘤有效。
The reason why small intestinal cancer is rarer than colorectal cancer is not clear. We hypothesized that intraepithelial lymphocytes (IELs), which are enriched in the small intestine, are the closest immune cells to epithelial cells, exclude tumor cells via cell-to-cell contact. We developed DPE-green fluorescent protein (DPE-GFP) × adenomatous polyposis coli; multiple intestinal neoplasia (APCmin ) mice, which is a T-cell–reporter mouse with spontaneous intestinal tumors. We visualized the dynamics of IELs in the intestinal tumor microenvironment and the interaction between IELs and epithelial cells, and the roles of cell-to-cell contact in anti-intestinal tumor immunity using a novel in vivo live-imaging system and a novel in vitro co-culture system. In the small intestinal tumor microenvironment, T-cell movement was restricted around blood vessels and the frequency of interaction between IELs and epithelial cells was reduced. Genetic deletion of CD103 decreased the frequency of interaction between IELs and epithelial cells, and increased the number of small intestinal tumors. In the co-culture system, wild-type IELs expanded and infiltrated to intestinal tumor organoids from APCmin mice and reduced the viability of them, which was cell-to-cell contact and CD103 dependent. The abundance of IELs in the small intestine may contribute to a low number of tumors, although this system may not work in the colon because of the sparseness of IELs. Strategies to increase the number of IELs in the colon or enhance cell-to-cell contact between IELs and epithelial cells may be effective for the prevention of intestinal tumors in patients with a high cancer risk.
登录
查看更多内容
DOI：
10.1084/jem.20061890
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Boissonnas A;Fetler L;Zeelenberg IS;Hugues S;Amigorena S
通讯作者：
Amigorena S
影响因子：
5.6
作者：
Schottenfeld D;Beebe-Dimmer JL;Vigneau FD
通讯作者：
Vigneau FD
影响因子：
11.2
作者：
Swamy, Malisetty V.;Patlolla, Jagan M. R.;Rao, Chinthalapally V.
通讯作者：
Rao, Chinthalapally V.
影响因子：
11.2
作者：
Rao, Varada P.;Poutahidis, Theofilos;Erdman, Susan E.
通讯作者：
Erdman, Susan E.
DOI：
10.1158/1078-0432.ccr-13-3173
发表时间：
2015-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jung HY;Fattet L;Yang J
通讯作者：
Yang J