Dynamic tracing of immune cells in an orthotopic gastric carcinoma mouse model using near-infrared fluorescence live imaging
Dynamic tracing of immune cells in an orthotopic gastric carcinoma mouse model using near-infrared fluorescence live imaging
复制标题
使用近红外荧光实时成像动态追踪原位胃癌小鼠模型中的免疫细胞
DOI：
10.3892/etm.2012.579
复制
发表时间：
2012-08-01
影响因子：
2.7
通讯作者：
Xu, Yingxin
中科院分区：
文献类型：
--
作者：
Du, Xiaohui;Wang, Xiangyu;Xu, Yingxin
过继细胞免疫疗法（ACI）已被证明是一种有前途的癌症治疗方法，然而，注射到荷瘤体内的免疫细胞的分布尚不清楚。在这项研究中，我们使用近红外荧光成像系统研究了人胃癌原位小鼠模型中细胞因子诱导的杀伤（CIK）细胞和细胞毒性T淋巴细胞（CTL）的肿瘤靶向能力。使用近红外荧光染料 DiR 制备 CIK 细胞和肿瘤特异性 CTL。正如预期的那样，用 DiR 标记后，CIK 细胞和 CTL 的增殖率或抗肿瘤活性没有显着变化。此外，采用纤维蛋白原-凝血酶法在裸鼠中建立胃癌原位模型，然后将标记的免疫细胞注射到已建立胃癌的裸鼠腹腔内。使用基于荧光的实时成像系统对免疫细胞进行动态追踪。在注射 CIK 细胞或 CTL 的小鼠中，在肿瘤部位观察到集中的荧光信号至少两周，并在 48 小时出现峰值信号。值得注意的是，输注后 CTL 在肿瘤部位更持久，并且比 CIK 细胞表现出更强的抗肿瘤活性。这些结果为活体动物中免疫细胞的肿瘤靶向能力提供了直观证据。
Adoptive cellular immunotherapy (ACI) has been demonstrated to be a promising cancer therapeutic, however, the distribution of immune cells injected into a tumor-bearing body is unclear. In this study, we investigated the tumor-targeting capacity of cytokine-induced killer (CIK) cells and cytotoxic T lymphocytes (CTLs) in a human gastric carcinoma orthotopic mouse model using a near-infrared fluorescence imaging system. CIK cells and tumor-specific CTLs were prepared with the near-infrared fluorescent dye DiR. As expected, no significant change in the proliferation rate or antitumor activity of CIK cells and CTLs was noted after labeling with DiR. Furthermore, a gastric carcinoma orthotopic model was established using a fibrinogen-thrombin method in nude mice followed by intraperitoneal infusion of the labeled immune cells into nude mice with established gastric carcinoma. Dynamic tracing of the immune cells was performed using a fluorescence-based live imaging system. Concentrated fluorescence signals were observed for a minimum of two weeks at the tumor site in mice infused with either CIK cells or CTLs with a peak signal at 48 h. Notably, CTLs were more persistent at the tumor site and exhibited a more intense antitumor activity than CIK cells following infusion. These results provided visual evidence of the tumor-targeting capacity of immune cells in live animals.