Genomic loss of mismatched human leukocyte antigen and leukemia immune escape from haploidentical graft-versus-leukemia.
Semin Oncol
; 39(6): 707-15, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-23206847
ABSTRACT
Recent developments in cell processing and immunosuppressive strategies has allowed the safe infusion of high numbers of donor T cells in the context of clinical haploidentical hematopoietic stem cell transplantation (HSCT). Haploidentical T cells display an intrinsic ability to recognize and eliminate residual patient leukemic cells, largely due to alloreactivity against the patient-specific human leukocyte antigen (HLA) molecules encoded on the mismatched haplotype. However, recent evidence has shown that leukemia, like many other tumors displaying pronounced genomic instability, is frequently able to evade this potent graft-versus-leukemia effect by undergoing de novo genomic mutations, which result in the permanent loss of only those HLA molecules targeted by haploidentical donor T-cell alloreactivity. This review summarizes the recent clinical and experimental evidence regarding this phenomenon, and its therapeutic and clinical consequences.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia
/
Transplante de Células-Tronco Hematopoéticas
/
Efeito Enxerto vs Leucemia
/
Evasão da Resposta Imune
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article