淋巴细胞性脉络膜脑膜炎
生物
胶质瘤
表位
免疫系统
免疫
免疫学
接种疫苗
抗原
CD8型
李斯特菌感染
细胞毒性T细胞
单核细胞增生李斯特菌
免疫疗法
病毒学
癌症研究
李斯特菌
体外
细菌
生物化学
遗传学
作者
Linda M. Liau,Eric L. N. Jensen,Thomas J. Kremen,Sylvia K. Odesa,Steven N. Sykes,Michael C. Soung,Jeff Miller,Jeff M. Bronstein
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2002-04-15
卷期号:62 (8): 2287-93
被引量:16
摘要
Tumors arising within the central nervous system (CNS) present the immune system with a challenging target, given the heterogeneous nature of these neoplasms and their location within an "immunologically privileged" site. We used the lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) as a pseudotumor antigen to investigate recombinant Listeria monocytogenes as a tumor vaccine against s.c. and intracerebral challenges with a NP-expressing glioma, 9L-NP. Using Fischer 344 rats, we demonstrate that vaccination with recombinant L. monocytogenes-NP stimulates protection against s.c., but not intracerebral, 9L-NP tumor challenge in an antigen-specific, CD8(+) T-cell-dependent manner. After s.c. tumor rejection, enhanced antitumor immunity is achieved via epitope spreading that permits complete resistance against lethal intracerebral challenge with 9L-NP and with the untransfected parental 9L tumor. Unlike the CD8(+)-dependent immune responses against s.c. 9L-NP tumors, this expanded intracerebral immunity against endogenous tumor-associated antigens is dependent on both CD4(+) and CD8(+) T cells. Taken together, these results demonstrate that the mechanisms of tumor immunity within the brain are different from those elicited against non-CNS tumors. Furthermore, vaccination approaches exploiting the concept of epitope spreading may enhance the efficacy of antitumor immune responses within the immunologically privileged CNS, potentially mediating tumor cell killing through both CD4(+)- and CD8(+)-dependent effector pathways.
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