T细胞和TIDC细胞与肿瘤生长和转移的关系

T cells and TIDC in relation to tumor growth and metastasis

目的利用Lewis肺癌动物模型(Lewis模型)探讨T细胞和肿瘤浸润树突状细胞的分布和浸润情况在肿瘤的生长和转移中的作用。方法实验性研究。采用42只C57BL/6小鼠建立Lewis模型,并随机分为T细胞组、肿瘤浸润树突状细胞组和对照组,每组14只。各组分别回输CD4^(+)CD8^(+)Treg细胞、肿瘤浸润树突状细胞和等量PBS,于1、5、9、13、17、21 d,用游标卡尺测量瘤体最长直径和最短直径,计算瘤体积,并记录小鼠的生存状态;流式细胞技术检测肿瘤微环境中CD4^(+)、CD8^(+)T细胞和肿瘤浸润树突状细胞的水平;HE组织染色技术判明肺部转移性肿瘤结节。结果3组小鼠肿瘤体积均有增长,且T细胞组>TIDC细胞组>对照组,差异有统计学意义(P值均<0.05);流式结果显示,Lewis模型的效应和记忆效应CD4^(+)CD8^(+)T细胞和肿瘤浸润树突状细胞在总淋巴细胞中的比例,T细胞组高于对照组和肿瘤浸润树突状细胞组,肿瘤浸润树突状细胞组高于对照组,差异均有统计学意义(P值均<0.05);回输CD4^(+)CD8^(+)Treg细胞及TIDC细胞后,小鼠肺部转移性肿瘤结节数量显著增多,T细胞组>肿瘤浸润树突状细胞组>对照组。分别为T细胞组(4.47±0.68)个,TIDC组(2.43±0.46)个,对照组(1.72±0.32)个,差异有统计学意义(P值均<0.05)。结论Lewis肺癌生长速度可能与CD4^(+)CD8^(+)Treg细胞和肿瘤浸润树突状细胞的分布情况有关,其分布程度越高,肿瘤生长越快。

Objective To investigate the role of the distribution and infiltration of T cells and tumor-infiltrating dendritic cells(TIDC)in the growth and metastasis of lung cancer by using Lewis lung cancer subcutaneous transplantation tumor model(Lewis model).Methods This was an experimental research.Lewis model was established by 42 C57BL/6 adult mice which were randomly divided into the T cell group,TIDC group and control group(n=14).The three groups were respectively reinfused with CD4^(+)CD8^(+)Treg cells,TIDC and PBS.On days 1,5,9,13,17,and 21,the longest and shortest diameters of the tumor were measured with vernier calipers,the tumor volume was calculated,and the survival status of the mice was recorded.Flow cytometry was used to detect CD4^(+),CD8^(+)T cells and TIDC in the tumor microenvironment.HE tissue staining was performed to identify pulmonary metastatic tumor nodules.Results The tumor volume of mice increased in all three groups T cells group>tumor-infiltrating dendritic cells group>control group,the difference was statistically significant(P<0.05).Flow cytometry results showed that the proportion of CD4^(+)T cells,CD8^(+)T cells and TIDC in total lymphocyte of Lewis model were significantly different,and T cell group>TIDC group>control group(P<0.05).After the mice was reinfusd by CD4^(+)CD8^(+)Treg cells and TIDC,the number of pulmonary metastatic tumor nodules in mice increased significantly,T cells group>tumor-infiltrating dendritic cells group>control group.The differences were statistically significant in T-cell group(4.47±0.68),TIDC group(2.43±0.46)and control group(1.72±0.32).Conclusions The growth rate of Lewis lung cancer may be related to the distribution of CD4^(+)CD8^(+)Treg cells and TIDC.The higher the distribution,the faster the tumor growth.