Enhancement of antitumor immunity by CTLA-4 blockade
Enhancement of antitumor immunity by CTLA-4 blockade
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DOI：
10.1126/science.271.5256.1734
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发表时间：
1996-03-22
期刊：
影响因子：
56.9
通讯作者：
Allison, JP
中科院分区：
文献类型：
--
作者：
Leach, DR;Krummel, MF;Allison, JP
许多肿瘤免疫原性差的一个原因可能是它们不能提供完全激活T细胞所必需的CD 28介导的共刺激信号。最近已经变得明显的是，CTLA-4，共刺激分子的B7家族的第二反受体，是T细胞活化的负调节剂。在此，体内施用CTLA-4抗体导致肿瘤排斥，包括预先建立的肿瘤。此外，这种排斥导致对二次暴露于肿瘤细胞的免疫力。这些结果表明，阻断CTLA-4的抑制作用可以允许并加强针对肿瘤细胞的有效免疫应答。
One reason for the poor immunogenicity of many tumors may be that they cannot provide signals for CD28-mediated costimulation necessary to fully activate T cells. It has recently become apparent that CTLA-4, a second counterreceptor for the B7 family of costimulatory molecules, is a negative regulator of T cell activation. Here, in vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors. Furthermore, this rejection resulted in immunity to a secondary exposure to tumor cells. These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells.