体内阻断细胞毒性T淋巴细胞相关抗原4（CTLA-4）可增强反应性T细胞的致敏，但无法阻止肿瘤抗原特异性耐受性的诱导。
In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance.
作者信息
Sotomayor E M, Borrello I, Tubb E, Allison J P, Levitsky H I
机构信息
Department of Oncology, Johns Hopkins University, Baltimore, MD 21205, USA.
出版信息
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11476-81. doi: 10.1073/pnas.96.20.11476.
Abstract
The efficacy of therapeutic vaccination for the treatment of cancer is limited by peripheral tolerance to tumor antigens. In vivo blockade of CTLA-4, a negative regulator of T cell function, can induce the regression of established tumors and can augment the tumor rejection achieved through therapeutic vaccination. These outcomes may reflect enhanced tumor-specific T cell priming and/or interference with the development of tolerance to tumor antigens. We examined the effect of CTLA-4 blockade on the fate and function of T cells specific for a model tumor antigen in the tumor-bearing host. We found that while CTLA-4 blockade enhanced the priming of responsive T cells, it did not prevent the induction of tolerance to tumor antigens. These results demonstrate that there is a critical window in which the combination of CTLA-4 blockade and vaccination achieves an optimal response, and they point to mechanisms other than CTLA-4 engagement in mediating peripheral T cell tolerance to tumor antigens.
摘要
治疗性疫苗治疗癌症的疗效受到对外周肿瘤抗原耐受性的限制。体内阻断T细胞功能的负调节因子CTLA-4，可诱导已形成肿瘤的消退，并可增强通过治疗性疫苗实现的肿瘤排斥反应。这些结果可能反映了肿瘤特异性T细胞致敏增强和/或对肿瘤抗原耐受性发展的干扰。我们研究了CTLA-4阻断对荷瘤宿主中模型肿瘤抗原特异性T细胞命运和功能的影响。我们发现，虽然CTLA-4阻断增强了反应性T细胞的致敏，但它并不能阻止对肿瘤抗原耐受性的诱导。这些结果表明，存在一个关键窗口期，在此期间CTLA-4阻断和疫苗接种的联合可实现最佳反应，并且它们指出了除CTLA-4参与介导外周T细胞对肿瘤抗原耐受性之外的其他机制。
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