Vierboom M P, Zwaveling S, Ooms M, Krietemeijer G M, Melief C J, Offringa R
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands.
Cancer Res. 2000 Oct 1;60(19):5508-13.
CTLs specific to p53 were previously shown to efficiently eradicate p53-overexpressing tumor cells in vitro as well as in vivo. In this report, we demonstrate that these CTLs can also eliminate tumors that display moderate or even low levels of p53. Neither high steady-state levels of p53 nor elevated p53 synthesis is a prerequisite for recognition of tumors by p53-specific CTLs. Instead, our data show that a high p53 turnover rate is an important factor in determining the sensitivity of tumor cells to p53-specific CTLs. Our data suggest that p53 turnover is related to the MHC class I-restricted presentation of p53-derived epitopes at the tumor cell surface and indicate that CTL-mediated immunotherapy that targets p53 can be applied to a wider range of tumors than has thus far been anticipated.
先前已表明，对p53特异的细胞毒性T淋巴细胞（CTL）在体外以及体内均能有效根除过表达p53的肿瘤细胞。在本报告中，我们证明这些CTL也能消除显示中等甚至低水平p53的肿瘤。高稳态水平的p53和升高的p53合成均不是p53特异的CTL识别肿瘤的先决条件。相反，我们的数据表明，高p53周转速率是决定肿瘤细胞对p53特异的CTL敏感性的一个重要因素。我们的数据提示，p53周转与肿瘤细胞表面MHC I类限制性p53衍生表位的呈递有关，并表明靶向p53的CTL介导的免疫疗法可应用于比迄今预期更广泛的肿瘤。
