Detección de linfocitos T citotóxicos contra los epítopos 264-272 y 149-157 de la proteína p53 en sangre periférica de pacientes con cáncer de mama

Abstract

p53 protein is overexpressed in nearly half of all human tumours. An HLA-A2.1-restricted immunological response mediated by anti-p53 CD8+ T cells directed against the wild type p53 264-272 epitope has been demonstrated in patients with head and neck squamous carcinomas. The existence of such a response in patients with other cancer types could be determinant for the development of specific antitumour vaccines targeting the p53 protein. We aimed to determine the presence of anti-p53 specific CD8+ T cells in peripheral blood of breast cancer patients in vivo. p53 264-272-specific CD8+ T cells were directly enumerated in the peripheral circulation of patients with breast cancer using tetrameric p53 264-272/HLA-A2.1 complexes by multicolor flow cytometry. The same procedure was used to enumerate T cells specific for another HLA-A2.1 restricted wild type p53 epitope, p53 (149-157). The 99th percentile of the concentration of anti-p53 cells in 6 HLA A2- breast cancer patients was 1/5634 (cut-off point). The median counts of anti-p53264-272 and anti-p53149-157 lymphocytes in 14 HLA A2.1+ patients were 1/2383 and 1/2335 respectively. All of the HLA A2+ patients had concentrations of anti-p53 lymphocytes above the cut-off point for at least one of the epitopes: 13/14 (93%) for p53(264-272) and 11/12 (92%) for p53(149-157). A specific immunological response mediated by anti-p53 CD8+ T cells has been detected in patients with breast carcinoma. More studies are needed to confirm these results and to determine its usefulness for the development of p53-based vaccines.