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Analysis of the mechanism of inhibition of liver metastasis from colon cancer ------The role of Interleukin 2 receptor of the liver sinusoidal mononuclear cells

抑制结肠癌肝转移的机制分析------白细胞介素2受体对肝窦单个核细胞的作用

基本信息

批准号：
08457337
负责人：
NAKAMURA Yoshiaki
金额：
$ 4.86万
依托单位：
TAZUKE KOFUKAI MEDICAL RESEARCH INSTITUTE.
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至无数据
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457337/
关键词：
colon cancer liver metastasis liver sinusoidal monounclear cell CD3 CD56 IL-2 receptor immuno-chemotherapy CEA

项目摘要

[Purpose] in this study, we studied the characters of SMC and PBMC,based on the hypothesis that the immune system managed by sinusoidal mononuclear cells (SMC) was damaged in the patient bearing metastatic liver cancer (MLC).[Materials and methods] We analyzed the surface antigens on SMC and PBMC by flowcytometry in seven liver specimens taken from hepatectomized patients with MLC.The patients were aged from 35 to 80,4males and 3 females. Primary lesions were cecum (2), ascending colon (2) and 3 sigmoid colon (3). In the control group, we analized PBMC of healthy candidates. Response against IL-2 was assesed by MTT assay.[Results] In MLC patients, CD3 (+) T cell decreased to 30 % (50-60% : normal) in PMBC and 40% (50% : normal) in SMC.CD16 (+) NK cells increased to 25-69% (20% : normal). Abnormal CD4/CD8 ratio in PBMC were observed in three cases, who showed high CEA value.CD8 and CD56 double positive cells were decresed below 30% in comparison with normal SMC (50%). IL-2R alpha chain was induced, but IL-2R beta chain was not recognized even after IL-2 stimulation.[Conclusion] In MLC,CTL cells were decreased in SMC,especially in the high CEA value patients, showng the possibility of lower immunological defense ability than normal. The lower responsiveness to IL-2 in CTL was also recognized. It may be effective that the immuno-chemothrapy by injection via hepatic artery or portal vein using anti-cancer drugs and additional IL-2. This therapy will increase the CTL cells in SMC and make a good control in IL-2 R system, affecting the excellent results for the therapy in liver metastasis patients.

[目的]本研究基于肝窦单核细胞（SMC）管理的免疫系统在转移性肝癌（MLC）患者中受损的假设，研究SMC和PBMC的特征。 [材料与方法]采用流式细胞术分析7例肝切除患者肝脏标本中SMC和PBMC的表面抗原。 MLC。患者年龄35～80岁，男4例，女3例。主要病变为盲肠（2）、升结肠（2）和第三乙状结肠（3）。在对照组中，我们分析了健康受试者的 PBMC。通过MTT测定评估针对IL-2的反应。 [结果] 在MLC患者中，PMBC中CD3(+)T细胞减少至30%(50-60%：正常)，SMC中CD3(+)T细胞减少至40%(50%：正常)。CD16(+)NK细胞增加至25-69%(20%：正常)。 3例PBMC中CD4/CD8比值异常，CEA值较高。与正常SMC（50%）相比，CD8、CD56双阳性细胞减少至30%以下。 IL-2Rα链被诱导，但IL-2Rβ链在IL-2刺激后仍不被识别。[结论]在MLC中，SMC中CTL细胞减少，特别是在高CEA值患者中，表现出免疫防御能力低于正常人的可能性。还认识到 CTL 对 IL-2 的反应性较低。通过肝动脉或门静脉注射抗癌药物和额外的IL-2进行免疫化疗可能是有效的。该疗法会增加SMC中的CTL细胞，并对IL-2R系统进行良好的控制，影响肝转移患者治疗的良好效果。