Ramarathinam L, Sarma S, Maric M, Zhao M, Yang G, Chen L, Liu Y
Michael Heidelberger Division of Immunology, Department of Pathology, New York University Medical Center, New York 10016, USA.
J Immunol. 1995 Dec 1;155(11):5323-9.
Whether tumors of different lineages share common Ags is a critical issue for understanding anti-tumor immune responses and for designing Ag-specific tumor immunotherapy. Because of lack of cross-protection among individually derived tumors, it has been proposed that tumor Ags are specific for individual tumors. Here we show that lack of cross-protection is not due to lack of a shared tumor Ag. Thus, a plasmocytoma J558 transfected with the costimulatory molecule B7 activates a cross-reactive CTL response in vivo. The major Ag recognized by the cross-reactive CTL is P1A, which is expressed in mastocytoma P815, plasmocytoma J558, and fibrosarcoma Meth A. Surprisingly, no significant cross-protection can be detected among P1A-expressing tumors after immunization with either P1A-expressing or B7-transfected P815 cells. Our results demonstrate that multiple lineages of tumors are not cross-protected even though they share a tumor Ag that can be recognized by CTL. These results have important implications for tumor immunotherapy.
不同谱系的肿瘤是否共享共同抗原,这对于理解抗肿瘤免疫反应以及设计抗原特异性肿瘤免疫疗法而言是一个关键问题。由于个体来源的肿瘤之间缺乏交叉保护作用,因此有人提出肿瘤抗原是个体肿瘤特有的。在此我们表明,缺乏交叉保护并非由于缺乏共享的肿瘤抗原。因此,转染了共刺激分子B7的浆细胞瘤J558在体内激活了交叉反应性CTL应答。交叉反应性CTL识别的主要抗原是P1A,其在肥大细胞瘤P815、浆细胞瘤J558和纤维肉瘤Meth A中表达。令人惊讶的是,在用表达P1A或转染了B7的P815细胞免疫后,在表达P1A的肿瘤之间未检测到明显的交叉保护作用。我们的结果表明,即使多个谱系的肿瘤共享一种可被CTL识别的肿瘤抗原,它们之间也没有交叉保护作用。这些结果对肿瘤免疫疗法具有重要意义。