Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Leukemia ; 32(2): 429-437, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28676668

RESUMO

The calreticulin (CALR) exon 9 mutations are found in ∼30% of patients with essential thrombocythemia and primary myelofibrosis. Recently, we reported spontaneous immune responses against the CALR mutations. Here, we describe that CALR-mutant (CALRmut)-specific T cells are able to specifically recognize CALRmut cells. First, we established a T-cell culture specific for a CALRmut epitope. These specific T cells were able to recognize several epitopes in the CALRmut C terminus. Next, we established a CALRmut-specific CD4+ T-cell clone by limiting dilution. These CD4+ T cells recognized autologous CALRmut monocytes and hematopoietic stem cells, and T-cell recognition of target cells was dependent on the presence of CALR. Furthermore, we showed that the CALRmut response was human leukocyte antigen (HLA)-DR restricted. Finally, we demonstrated that the CALRmut-specific CD4+ T cells, despite their phenotype, were cytotoxic to autologous CALRmut cells, and that the cytotoxicity was mediated by degranulation of the T cells. In conclusion, the CALR exon 9 mutations are targets for specific T cells and thus are promising targets for cancer immune therapy such as peptide vaccination in patients harboring CALR exon 9 mutations.


Assuntos
Calreticulina/genética , Éxons/efeitos dos fármacos , Mutação/efeitos dos fármacos , Neoplasias/genética , Neoplasias/terapia , Vacinas de Subunidades Antigênicas/uso terapêutico , Idoso , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Citotoxicidade Imunológica/efeitos dos fármacos , Éxons/genética , Antígenos HLA/efeitos dos fármacos , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Masculino , Mutação/genética , Neoplasias/imunologia , Fenótipo , Mielofibrose Primária/genética , Mielofibrose Primária/imunologia , Trombocitemia Essencial/genética , Trombocitemia Essencial/imunologia , Vacinas de Subunidades Antigênicas/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...