[Detection of specific T cells for 264-272 and 149-157 peptides of p53 protein in peripheral blood of patients with breast cancer]. / 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.

BACKGROUND AND OBJECTIVE: 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. PATIENTS AND METHOD: 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). RESULTS: 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). CONCLUSIONS: 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.

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 / Detection of specific T cells for 264-272 and 149-157 peptides of p53 protein in peripheral blood of patients with breast cancer

FUNDAMENTO Y OBJETIVO: La proteína p53 está sobreexpresada en la mitad de los tumores humanos.Se ha descrito que se produce una respuesta inmunológica específica mediada por linfocitosT citotóxicos dirigidos contra el epítopo 264-272 de p53 en pacientes con cáncer de cabezay cuello. Demostrar que se produce ese tipo de respuesta en otros tumores podría serdeterminante para el desarrollo de vacunas antitumorales específicas anti-p53. El objetivo deeste estudio fue demostrar in vivo la existencia de linfocitos T citotóxicos específicos anti-p53en sangre periférica de pacientes con cáncer de mama.PACIENTES Y MÉTODO: Se realizó la determinación mediante citometría de flujo del recuento delinfocitos T citotóxicos específicos dirigidos contra los epítopos HLA A2 restringidos 264-272 y149-147 de la proteína p53 en sangre periférica de pacientes con cáncer de mama.RESULTADOS: El percentil 99 de la concentración de células T anti-p53 en los pacientes conHLA A2.1 negativo fue 1/5.634 (punto de corte). En los pacientes con HLA A2 positivo, la medianade linfocitos anti-p53264-272 fue de 1/2.383 y la de linfocitos anti-p53149-157, de 1/2.335.Todos los pacientes con HLA A2 positivo presentaron recuentos de linfocitos anti-p53 por encimadel punto de corte para al menos uno de los 2 epítopos: 13/14 (93%) para p53264-272 y11/12 (92%) para p53149-157.CONCLUSIONES: Ha sido posible demostrar in vivo que hay una respuesta inmunológica específicamediada por linfocitos T citotóxicos anti-p53 en pacientes con cáncer de mama. Son necesariosfuturos estudios para confirmar estos resultados y determinar su utilidad para el diseño y eldesarrollo de vacunas dirigidas contra la proteína p53

BACKGROUND AND OBJECTIVE: p53 protein is overexpresed in nearly half of all human tumours. AnHLA-A2.1-restricted immunological response mediated by anti-p53 CD8+ T cells directedagainst the wild type p53 264-272 epitope has been demonstrated in patients with head andneck squamous carcinomas. The existence of such a response in patients with other cancer typescould be determinant for the development of specific antitumour vaccines targeting thep53 protein. We aimed to determine the presence of anti-p53 specific CD8+ T cells in peripheralblood of breast cancer patients in vivo.PATIENTS AND METHOD: p53 264-272-specific CD8+ T cells were directly enumerated in the peripheralcirculation of patients with breast cancer using tetrameric p53 264-272/HLA-A2.1complexes by multicolor flow cytometry. The same procedure was used to enumerate T cellsspecific for another HLA-A2.1 restricted wild type p53 epitope, p53 (149-157).RESULTS: The 99th percentile of the concentration of anti-p53 cells in 6 HLA A2– breast cancerpatients was 1/5634 (cut-off point). The median counts of anti-p53264-272 and anti-p53149-157lymphocytes in 14 HLA A2.1+ patients were 1/2383 and 1/2335 respectively. All of the HLAA2+ patients had concentrations of anti-p53 lymphocytes above the cut-off point for at leastone of the epitopes: 13/14 (93%) for p53264-272 and 11/12 (92%) for p53149-157.CONCLUSIONS: A specific immunological response mediated by anti-p53 CD8+ T cells has beendetected in patients with breast carcinoma. More studies are needed to confirm these resultsand to determine its usefulness for the development of p53-based vaccines