Mechanisms of Leukemia Immune Evasion and Their Role in Relapse After Haploidentical Hematopoietic Cell Transplantation.

Frontiers in Immunology
Pier Edoardo RovattiLuca Vago

Abstract

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 int...Continue Reading

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Methods Mentioned

BETA
chromosomal aberration
PCR
xenografts
glycosylation

Clinical Trials Mentioned

NCT02890329
NCT02845297
NCT02996474
NCT02397720

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