Williams S S, Chen F A, Kida H, Yokata S, Miya K, Kato M, Barcos M P, Wang H Q, Alosco T, Umemoto T, Croy B A, Repasky E A, Bankert R B
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
J Immunol. 1996 Mar 1;156(5):1908-15.
We report here the placement of nondisrupted 1-mm3 pieces of fresh human lung tumor biopsy tissue into the subcutis of severe combined immunodeficient (SCID) mice results in the engraftment of tumor-infiltrating leukocytes (TIL) in all but 5 of 148 mice inoculated with 39 different biopsy tissue specimens. In mice coengrafted with tumor and TIL the normal histologic architecture of the tumor and TIL interface was maintained for up to 22 wk. The TIL in the xenograft were shown to divide and were maintained exclusively at the site of tumor inoculation. It is established here that plasma cells in the TIL population produce Abs that react in western blots with tumor cell lysates. These Abs were shown to react with high and low m.w. proteins derived from both the membrane and cytosolic fractions of tumor cell lysates. The production of human Ig was found to be T cell dependent, and immunohistochemistry and in situ hybridization of DNA, using a human-specific cDNA probe, established the human identity of the tumor and TIL. High levels of human Ig in the sera of mice inoculated with tumor biopsy tissue are associated with the growth arrest of adenocarcinoma xenografts. Our results establish the co-engraftment of human tumors and TIL into SCID mice as new animal model with which to evaluate TIL function and novel therapeutic strategies that are designed to augment TIL anti-tumor activity.
我们在此报告，将未受破坏的1立方毫米新鲜人肺肿瘤活检组织植入严重联合免疫缺陷（SCID）小鼠的皮下后，在接种39种不同活检组织标本的148只小鼠中，除5只外，其余小鼠的肿瘤浸润白细胞（TIL）均实现了植入。在同时植入肿瘤和TIL的小鼠中，肿瘤与TIL界面的正常组织学结构维持了长达22周。异种移植中的TIL显示出可分裂，且仅在肿瘤接种部位维持存在。在此证实，TIL群体中的浆细胞产生的抗体在蛋白质印迹中与肿瘤细胞裂解物发生反应。这些抗体显示出与源自肿瘤细胞裂解物膜和胞质部分的高分子量和低分子量蛋白质发生反应。发现人Ig的产生依赖于T细胞，并且使用人特异性cDNA探针进行的DNA免疫组织化学和原位杂交确定了肿瘤和TIL的人源特性。接种肿瘤活检组织的小鼠血清中高水平的人Ig与腺癌异种移植的生长停滞相关。我们的结果确立了将人肿瘤和TIL共同植入SCID小鼠作为一种新的动物模型，可用于评估TIL功能以及旨在增强TIL抗肿瘤活性的新型治疗策略。
