Treatment of murine gliomas by adoptive transfer of ex vivo activated tumor-draining lymph node cells.
Treatment of murine gliomas by adoptive transfer of ex vivo activated tumor-draining lymph node cells.
复制标题
DOI：
10.1006/cimm.1997.1140
复制
发表时间：
1997-06
影响因子：
4.3
通讯作者：
G. Plautz;Joseph E. Touhalisky;Suyu Shu
中科院分区：
文献类型：
--
作者：
G. Plautz;Joseph E. Touhalisky;Suyu Shu
肿瘤反应性T淋巴细胞的过继转移最近被证明是介导实验性颅内纤维肉瘤消退的有效手段。在这项研究中，小鼠携带同基因颅内GL 261胶质瘤治愈的亚致死全身照射，然后静脉转移的肿瘤引流淋巴结（LN）T细胞激活抗CD 3或葡萄球菌肠毒素C2（SEC 2）的组合。为了进一步鉴定过继免疫治疗中的功能性效应T细胞群，基于细胞粘附分子CD 62 L（L-选择素）的表达水平，将LN T细胞分成两个亚群。少至5 × 10（5）个CD 62 L低细胞可以治愈大多数动物，而2 × 10（6）个CD 62 L高细胞完全无效。此外，从晚期颅内肿瘤中分离的T细胞被鉴定为主要是CD 62 Llow。相反，脾脏含有与转移的细胞群相似的CD 62 L低和高细胞的混合物。胶质瘤部位的T细胞比从脾脏分离的T细胞增殖更活跃。治愈GL 261肿瘤的小鼠通过拒绝原始肿瘤的颅内挑战而不是免疫学上不同的肿瘤表现出长期免疫记忆。此外，尽管转移的细胞浸润到颅内肿瘤中，但治愈的小鼠在治疗期间、长期随访期间或颅内肿瘤再激发后未表现出任何明显的神经系统异常。本研究证明了通过活化的肿瘤引流LN T细胞的系统过继转移和治疗活性的CD 62 Llow T细胞的选择性肿瘤浸润来有效治疗颅内鼠胶质瘤。
The adoptive transfer of tumor-reactive T lymphocytes has recently been demonstrated to be an effective means for mediating the regression of experimental intracranial fibrosarcomas. In this study, mice bearing syngeneic intracranial GL261 gliomas were cured by the combination of sublethal whole body irradiation followed by the intravenous transfer of tumor-draining lymph node (LN) T cells activated with anti-CD3 or staphylococcal enterotoxin C2 (SEC2). To further identify the functional effector T cel population in the adoptive immunotherapy, LN T cells were separated into two subsets, based on the level of expression of the cell adhesion molecule CD62L (L-selectin). As few as 5 x 10(5) CD62Llow cells could cure the majority of animals, whereas 2 x 10(6) CD62Lhigh cells were completely ineffective. Moreover, T cells isolated from advanced intracranial tumors were identified to be predominantly CD62Llow. In contrast, spleens contained a mixture of CD62L low and high cells similar to the transferred cell population. T cells in the glioma site were more actively proliferating than those isolated from the spleen. Mice cured of GL261 tumors demonstrated long-term immunologic memory by rejecting intracranial challenges of the original tumor but not an immunologically distinct tumor. Furthermore, despite infiltration of transferred cells into the intracranial tumors, cured mice did not exhibit any apparent neurologic abnormalities during treatment, prolonged follow-up, or after intracranial tumor rechallenge. This study demonstrates the effective treatment of an intracranial murine glioma by the systemic adoptive transfer of activated tumor-draining LN T cells and selective tumor infiltration by the therapeutically active CD62Llow T cells.