Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, 26 Yuancunerheng Road, Guangzhou 510655, PR China.
J Gastrointest Surg. 2013 Jul;17(7):1283-91. doi: 10.1007/s11605-013-2194-5. Epub 2013 May 14.
The local and systemic regulation of the immune system may play important roles in the process of liver metastasis of colorectal carcinoma. The aim of this study was to establish a reproducible experimental liver metastasis model, to identify changes in T cells and cytokines TGF-β1 and IL-10, and to explore a possible mechanism of liver metastasis of colon carcinoma.
We used a colon carcinoma liver metastasis model, in which different numbers of CT-26 murine colon carcinoma cells (1 × 10(3), 5 × 10(3), 1 × 10(4), 5 × 10(4), and 1 × 10(5)) were injected into the spleen. The liver and spleen tissues were examined for T cell markers using flow cytometry. Liver tissues were analyzed for IL-10 and transforming growth factor beta 1 (TGF-β1) expression using immunohistochemistry.
Spleen injection of colon carcinoma cells is a reproducible animal model for liver metastases, which resulted in quantity-dependent metastatic growth. We provided a snapshot of the hepatic immune microenvironment in the mouse liver metastasis model. Injection of A large number of tumor cells (5 × 10(4) and 1 × 10 (5) ) decreased anti-tumor cell counts, such as CD4(+) and CD8(+) T cells, and increased immune-suppressive cell counts (CD4(+)CD25(+) Treg cells). In addition, the expression levels of immunosuppressive cytokines IL-10 and TGF-β1 were also increased with the number of tumor cells.
Changes in the systemic and local immunological environment contribute to immunological escape mechanisms during liver metastasis of colon carcinoma, and therapies aiming at immune microenvironment may prove a useful strategy in the treatment of metastatic disease in the future.
免疫系统的局部和全身调节可能在结直肠癌肝转移过程中发挥重要作用。本研究旨在建立一种可重复的实验性肝转移模型，以确定 T 细胞和细胞因子 TGF-β1、IL-10 的变化，并探讨结肠癌肝转移的可能机制。
我们使用结直肠癌肝转移模型，将不同数量的 CT-26 鼠结肠癌细胞（1×10(3)、5×10(3)、1×10(4)、5×10(4)和 1×10(5))注入脾脏。使用流式细胞术检测 T 细胞标志物。采用免疫组织化学法分析肝组织中白细胞介素 10 和转化生长因子β1（TGF-β1）的表达。
结肠癌细胞脾脏注射是一种可重现的肝转移动物模型，其转移生长具有数量依赖性。我们提供了小鼠肝转移模型中肝免疫微环境的快照。大量肿瘤细胞（5×10(4)和 1×10(5)）的注射降低了抗肿瘤细胞计数，如 CD4(+)和 CD8(+)T 细胞，并增加了免疫抑制性细胞计数（CD4(+)CD25(+)Treg 细胞）。此外，免疫抑制性细胞因子 IL-10 和 TGF-β1 的表达水平也随肿瘤细胞数量的增加而增加。
全身和局部免疫环境的变化有助于结直肠癌肝转移过程中的免疫逃逸机制，针对免疫微环境的治疗方法可能在未来成为转移性疾病治疗的一种有用策略。
