Tzeng J J, Barth R F, Orosz C G, James S M
Department of Pathology, Ohio State University, Columbus 43210.
Cancer Res. 1991 May 1;51(9):2373-8.
The purpose of the present study was to define the immunogenicity of two transplantable rat gliomas, designated F98 and D74, and to relate this to the phenotype and functional activity of tumor-infiltrating lymphocytes (TIL). Fischer rats, immunized with irradiated F98 tumor cells and challenged with intracerebral implants of ten F98 cells, had a median survival time of 49 days compared to 36 days for nonimmunized controls. In contrast, no statistically significant increases in survival times were noted in animals similarly immunized and challenged with the D74 tumors. No in vivo protection could be demonstrated in animals immunized and cross-challenged with either F98 or D74 glioma cells. Lymph node lymphocytes and TIL, isolated from animals immunized and challenged with F98 cells, were more cytolytically active than effector cells obtained from D74-immunized animals. Phenotypes of TIL isolated from intracerebral F98 gliomas of immunized rats were 52% OX-8+ and 21% W3/25+ compared to 31% OX-8+ and 19% W3/25+ for D74-immunized animals. Cytolytic activity against glioma targets was mediated by OX-8+ TIL, as determined by cell depletion experiments. Limiting dilution analysis showed that cytolytic T-lymphocyte precursors were present in TIL of F98 gliomas of immunized rats at a frequency of 1/3547 and were specific for F98 targets, while natural killer cell-like activity was low. Our data indicate that the F98 glioma was more immunogenic than the D74 glioma, as evidenced by increased numbers and activity of cytolytic effector cells and their precursors among TIL. This may explain in part the longer survival times observed in immunized animals challenged intracerebrally with the F98 gliomas compared to D74-immunized and -challenged hosts.
本研究的目的是确定两种可移植大鼠胶质瘤（分别命名为F98和D74）的免疫原性，并将其与肿瘤浸润淋巴细胞（TIL）的表型和功能活性相关联。用经照射的F98肿瘤细胞免疫并经脑内植入10个F98细胞攻击的Fischer大鼠，中位生存时间为49天，而未免疫对照组为36天。相比之下，用D74肿瘤进行类似免疫和攻击的动物，其生存时间没有统计学上的显著增加。在用F98或D74胶质瘤细胞免疫并交叉攻击的动物中，未证明有体内保护作用。从用F98细胞免疫并攻击的动物中分离出的淋巴结淋巴细胞和TIL，比从用D74免疫的动物获得的效应细胞具有更强的细胞溶解活性。从免疫大鼠脑内F98胶质瘤中分离出的TIL的表型为52% OX-8+和21% W3/25+，而用D74免疫的动物为31% OX-8+和19% W3/25+。通过细胞清除实验确定，对胶质瘤靶标的细胞溶解活性由OX-8+ TIL介导。有限稀释分析表明，免疫大鼠F98胶质瘤的TIL中细胞溶解T淋巴细胞前体的频率为1/3547，且对F98靶标具有特异性，而自然杀伤细胞样活性较低。我们的数据表明，F98胶质瘤比D74胶质瘤具有更强的免疫原性，TIL中细胞溶解效应细胞及其前体的数量和活性增加证明了这一点。这可能部分解释了与用D74免疫并攻击的宿主相比，用F98胶质瘤脑内攻击的免疫动物观察到的更长生存时间。
