Journal
BLOOD
Volume 110, Issue 6, Pages 1924-1932Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-03-076844
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Funding
- Medical Research Council [G0501963] Funding Source: Medline
- Medical Research Council [G0501963] Funding Source: researchfish
- MRC [G0501963] Funding Source: UKRI
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To determine whether the leukemia-associated Wilms tumor antigen (WT') contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL patients during the early phase of immune recovery after SCT (days 30-120). Seven of 10 patients had detectable WT1 expression in their peripheral blood (PB) before SCT by quantitative reverse-transcription polymerase chain reaction. Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining, WT1(+) CD8+ T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 31; P <.05). To monitor the kinetics of WT1(+) CD8+ T-cell responses and disease regression after SCT, absolute WT1(+) CD8+ T-cell numbers and WT1 expression were studied for each time point. The emergence of WT1(+) CD8+ T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect. Loss of WT1+ CD8+ T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P <.001). WT1+ CD8+ T cells had a predominantly effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma. Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.
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