Sun Hua-Wen, Wu Chong, Tan Hai-Yan, Wang Qiu-Shuang
Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Hepatogastroenterology. 2012 Nov-Dec;59(120):2677-82. doi: 10.5754/hge11620.
BACKGROUND/AIMS: Dendritic cells (DCs) are professional antigen-presenting cells responsible for initiating of immune response. However, because of immune tolerance, it is difficult to induce long-term tumor-specific immune response in humans. This is probably because DCs, which combine with Th2 in the Tim-1/Tim-4 pathway, will induce Th2 to proliferation.
We have transfected siRNA of FG-CC' gene into DCs stimulated by gastric cancer lysate (lysate-FG-CC-siRNA group), FG-CC-siRNA will block FG-CC' loop,which plays an important role in interaction between Tim-1 and Tim-4. Their potential effect on gastric cancer immunotherapy is assessed by an experimental model.
It was observed that lysate-FG-CC-siRNA had the strongest ability of adjusting balance on the Thl/Th2, as a result, these DCs can inhibit gastric cancer growth. In order to test the ability of FG-CC-siR-NA DCs to inhibit tumor growth, we immunized mice subcutaneously with DCs transfected with FG-CC-siR-NA plus tumor antigen. Compared with the control group, a significant inhibition of tumor growth was obvious for the group of lysate-FG-CC-siRNA DC.
We have shown that FG-CC-siRNA blocks FG-CC'loop and significantly enhances the anti-tumor immunity in vitro and in vivo.
背景/目的：树突状细胞（DCs）是负责启动免疫反应的专职抗原呈递细胞。然而，由于免疫耐受，在人类中难以诱导长期的肿瘤特异性免疫反应。这可能是因为在Tim-1/Tim-4途径中与Th2结合的DCs会诱导Th2增殖。
我们已将FG-CC'基因的小干扰RNA（siRNA）转染到由胃癌裂解物刺激的DCs中（裂解物-FG-CC-siRNA组），FG-CC-siRNA将阻断FG-CC'环，其在Tim-1和Tim-4之间的相互作用中起重要作用。通过实验模型评估它们对胃癌免疫治疗的潜在影响。
观察到裂解物-FG-CC-siRNA在调节Th1/Th2平衡方面具有最强的能力，因此，这些DCs可抑制胃癌生长。为了测试FG-CC-siRNA DCs抑制肿瘤生长的能力，我们用转染了FG-CC-siRNA加肿瘤抗原的DCs皮下免疫小鼠。与对照组相比，裂解物-FG-CC-siRNA DC组对肿瘤生长有明显的抑制作用。
我们已表明FG-CC-siRNA阻断FG-CC'环并在体外和体内显著增强抗肿瘤免疫力。
