High steady-state levels of p53 are not a prerequisite for tumor eradication by wild-type p53-specific cytotoxic T lymphocytes

CTLs specific to p53 were previously shown to efficiently eradicate p53-ove rexpressing tumor cells in vitro as well as in vivo. In this report, we dem onstrate that these CTLs can also eliminate tumors that display moderate or even low levels of p53, Neither high steady-state levels of p53 nor elevat ed p53 synthesis is a prerequisite for recognition of tumors by p53-specifi c CTLs. Instead, our data show that a high p53 turnover rate is an importan t 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-restrict ed presentation of p53-derived epitopes at the tumor cell surface and indic ate that CTL-mediated immunotherapy that targets p53 can be applied to a wi der range of tumors than has thus far been anticipated.