Fiche publication
Date publication
mai 2023
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FEUGIER Pierre
,
Pr RUBIO Marie Thérèse
,
Dr D'AVENI-PINEY Maud
,
Dr PAGLIUCA Simona
Tous les auteurs :
Pagliuca S, Gurnari C, Hercus C, Hergalant S, Hong S, Dhuyser A, D'Aveni M, Aarnink A, Rubio MT, Feugier P, Ferraro F, Carraway HE, Sobecks R, Hamilton BK, Majhail NS, Visconte V, Maciejewski JP
Lien Pubmed
Résumé
Graft-versus-leukemia (GvL) reactions are responsible for the effectiveness of allogeneic hematopoietic cell transplantation as a treatment modality for myeloid neoplasia, whereby donor T- effector cells recognize leukemia neoantigens. However, a substantial fraction of patients experiences relapses because of the failure of the immunological responses to control leukemic outgrowth. Here, through a broad immunogenetic study, we demonstrate that germline and somatic reduction of human leucocyte antigen (HLA) heterogeneity enhances the risk of leukemic recurrence. We show that preexistent germline-encoded low evolutionary divergence of class II HLA genotypes constitutes an independent factor associated with disease relapse and that acquisition of clonal somatic defects in HLA alleles may lead to escape from GvL control. Both class I and II HLA genes are targeted by somatic mutations as clonal selection factors potentially impairing cellular immune responses and response to immunomodulatory strategies. These findings define key molecular modes of post-transplant leukemia escape contributing to relapse.
Mots clés
Humans, Graft vs Host Disease, Leukemia, genetics, HLA Antigens, genetics, Chronic Disease, Hematopoietic Stem Cell Transplantation, adverse effects, Recurrence
Référence
Nat Commun. 2023 05 31;14(1):3153
