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-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.
Vierboom
M P
MP
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands.
Zwaveling
S
S
Bos GMJ
Ooms
M
M
Krietemeijer
G M
GM
Melief
C J
CJ
Offringa
R
R
D000256:Adenoviridae; D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016219:Immunotherapy, Adoptive; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016254:Mutagenesis, Insertional; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D027383:Papillomaviridae; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D017501:Adenovirus E1B Proteins; D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53