Surgical stress induces immunosuppression and this condition contributes to tumor growth

手术应激会引起免疫抑制，这种情况会导致肿瘤生长

• 批准号: 23591886
• 负责人: ONO Satoshi
• 金额: $ 3.33万
• 依托单位: National Defense Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591886/
• 关键词: 外科侵襲; 感染; 腫瘍免疫; 肝転移; NK細胞; 制御性T細胞; sepsis; IL-10; TGF-β; エンドトキシン吸着療法; Interleukin-18; IL-18受容体; IFN-γ

Recently, there has been increasing evidence that postoperative infectious complications after digestive surgery were significantly associated with negative long-term outcome. However, the precise mechanism remains unclear. We studied to determine whether the infection induces enhanced cancer metastases and to investigate the role of natural killer (NK) cells. Mice were treated with colon cancer cells, which have high potential liver metastases. Thereafter, cecal ligation and puncture (CLP) or sham treatment (sham) were done. As a result, the volume of liver metastases and serum cytokine levels were significantly higher in CLP mice than in sham mice. In contrast, hepatic IL-12 levels were significantly decreased in CLP mice. Furthermore, a total number of the liver MNCs and the percentage of NK cells in the liver MNCs were significantly decreased in CLP mice. In conclusion, infectious conditions induced the suppression of cellular immunity, and promoted cancer metastases.

近年来，越来越多的证据表明，消化道手术后的感染并发症与不良的长期预后显著相关。然而，确切的机制仍不清楚。我们研究以确定感染是否诱导增强的癌症转移，并调查自然杀伤（NK）细胞的作用。用结肠癌细胞治疗小鼠，结肠癌细胞具有高的肝转移潜力。此后，进行盲肠结扎和穿孔（CLP）或假处理（sham）。结果，CLP小鼠的肝转移灶体积和血清细胞因子水平显著高于假手术小鼠。相反，CLP小鼠的肝脏IL-12水平显著降低。此外，CLP小鼠肝脏MNCs的总数和肝脏MNCs中NK细胞的百分比显著降低。总之，感染条件诱导细胞免疫抑制，促进癌症转移。