Mechanisms of Leukemia Immune Evasion and Their Role in Relapse After Haploidentical Hematopoietic Cell Transplantation.
Animals
Cell- and Tissue-Based Therapy
/ methods
Graft vs Host Disease
/ therapy
Graft vs Leukemia Effect
Haplotypes
Hematopoietic Stem Cell Transplantation
/ adverse effects
Histocompatibility Antigens Class II
/ genetics
Humans
Immunotherapy
/ methods
Leukemia
/ immunology
Molecular Targeted Therapy
/ methods
Recurrence
T-Lymphocytes
/ immunology
Transplantation, Homologous
Tumor Escape
HLA
haploidentical allogeneic hematopoietic stem cell transplantation
immune check point
immune escape
relapse
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
04
10
2019
accepted:
20
01
2020
entrez:
12
3
2020
pubmed:
12
3
2020
medline:
9
3
2021
Statut:
epublish
Résumé
Over the last decade, the development of multiple strategies to allow the safe transfer from the donor to the patient of high numbers of partially HLA-incompatible T cells has dramatically reduced the toxicities of haploidentical hematopoietic cell transplantation (haplo-HCT), but this was not accompanied by a similar positive impact on the incidence of post-transplantation relapse. In the present review, we will elaborate on how the unique interplay between HLA-mismatched immune system and malignancy that characterizes haplo-HCT may impact relapse biology, shaping the selection of disease variants that are resistant to the "graft-vs.-leukemia" effect. In particular, we will present current knowledge on genomic loss of HLA, a relapse modality first described in haplo-HCT and accounting for a significant proportion of relapses in this setting, and discuss other more recently identified mechanisms of post-transplantation immune evasion and relapse, including the transcriptional downregulation of HLA class II molecules and the enforcement of inhibitory checkpoints between T cells and leukemia. Ultimately, we will review the available treatment options for patients who relapse after haplo-HCT and discuss on how a deeper insight into relapse immunobiology might inform the rational and personalized selection of therapies to improve the largely unsatisfactory clinical outcome of relapsing patients.
Identifiants
pubmed: 32158444
doi: 10.3389/fimmu.2020.00147
pmc: PMC7052328
doi:
Substances chimiques
Histocompatibility Antigens Class II
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
147Informations de copyright
Copyright © 2020 Rovatti, Gambacorta, Lorentino, Ciceri and Vago.
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