title: Genomic loss of mismatched human leukocyte antigen and leukemia immune escape from haploidentical graft-versus-leukemia.
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.
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milano, Italy. vago.luca@hsr.it
authors.forename: Luca
authors.initials: L
authors.lastname: Vago
authors.forename: Cristina
authors.initials: C
authors.lastname: Toffalori
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.forename: Katharina
authors.initials: K
authors.lastname: Fleischhauer
mesh_terms: D017951:Antigen Presentation; D020544:Graft vs Leukemia Effect / Q000235:genetics* / Q000276:immunology*; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D057131:Immune Evasion / Q000235:genetics* / Q000276:immunology*; D007938:Leukemia / Q000235:genetics* / Q000276:immunology* / Q000601:surgery; D014184:Transplantation, Homologous
chemical_list: D015395:Histocompatibility Antigens Class I