Myeloid leukemic progenitor cells can be specifically targeted by minor histocompatibility antigen LRH-1-reactive cytotoxic T cells.
Fulltext:
79829.pdf
Embargo:
until further notice
Size:
1.447Mb
Format:
PDF
Description:
Publisher’s version
Publication year
2009Source
Blood, 113, 10, (2009), pp. 2312-23ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Laboratory of Hematology
CHL
Paediatrics - OUD tm 2017
Haematology
Tumorimmunology
Journal title
Blood
Volume
vol. 113
Issue
iss. 10
Page start
p. 2312
Page end
p. 23
Subject
NCMLS 2: Immune Regulation; ONCOL 3: Translational researchAbstract
CD8(+) T cells recognizing minor histocompatibility antigens (MiHAs) on leukemic stem and progenitor cells play a pivotal role in effective graft-versus-leukemia reactivity after allogeneic stem cell transplantation (SCT). Previously, we identified a hematopoiesis-restricted MiHA, designated LRH-1, which is presented by HLA-B7 and encoded by the P2X5 purinergic receptor gene. We found that P2X5 is significantly expressed in CD34(+) leukemic subpopulations from chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) patients. Here, we demonstrate that LRH-1-specific CD8(+) T-cell responses are frequently induced in myeloid leukemia patients following donor lymphocyte infusions. Patients with high percentages of circulating LRH-1-specific CD8(+) T cells had no or only mild graft-versus-host disease. Functional analysis showed that LRH-1-specific cytotoxic T lymphocytes (CTLs) isolated from 2 different patients efficiently target LRH-1-positive leukemic CD34(+) progenitor cells from both CML and AML patients, whereas mature CML cells are only marginally lysed due to down-regulation of P2X5. Furthermore, we observed that relative resistance to LRH-1 CTL-mediated cell death due to elevated levels of antiapoptotic XIAP could be overcome by IFN-gamma prestimulation and increased CTL-target ratios. These findings provide a rationale for use of LRH-1 as immunotherapeutic target antigen to treat residual or persisting myeloid malignancies after allogeneic SCT.
This item appears in the following Collection(s)
- Academic publications [245054]
- Electronic publications [132354]
- Faculty of Medical Sciences [93209]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.