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- Title
PR1-Specific T Cells Are Associated with Unmaintained Cytogenetic Remission of Chronic Myelogenous Leukemia After Interferon Withdrawal.
- Authors
Kanodia, Shreya; Wieder, Eric; Lu, Sijie; Talpaz, Moshe; Alatrash, Gheath; Clise-Dwyer, Karen; Molldrem, Jeffrey J.
- Abstract
Background: Interferon-α (IFN) induces complete cytogenetic remission (CCR) in 20-25% CML patients and in a small minority of patients; CCR persists after IFN is stopped. IFN induces CCR in part by increasing cytotoxic T lymphocytes (CTL) specific for PR1, the HLA-A2-restricted 9-mer peptide from proteinase 3 and neutrophil elastase, but it is unknown how CCR persists after IFN is stopped. Principal Findings: We reasoned that PR1-CTL persist and mediate CML-specific immunity in patients that maintain CCR after IFN withdrawal. We found that PR1-CTL were increased in peripheral blood of 7/7 HLA-A2+ patients during unmaintained CCR from 3 to 88 months after IFN withdrawal, as compared to no detectable PR1-CTL in 2/2 IFN-treated CML patients not in CCR. Unprimed PR1-CTL secreted IFNγ and were predominantly CD45RA±CD28+CCR7+CD57-, consistent with functional naïve and central memory (CM) T cells. Similarly, following stimulation, proliferation occurred predominantly in CM PR1-CTL, consistent with long-term immunity sustained by self-renewing CM T cells. PR1-CTL were functionally anergic in one patient 6 months prior to cytogenetic relapse at 26 months after IFN withdrawal, and in three relapsed patients PR1-CTL were undetectable but re-emerged 3-6 months after starting imatinib. Conclusion: These data support the hypothesis that IFN elicits CML-specific CM CTL that may contribute to continuous CCR after IFN withdrawal and suggest a role for T cell immune therapy with or without tyrosine kinase inhibitors as a strategy to prolong CR in CML.
- Subjects
T cells; CHRONIC myeloid leukemia; DISEASE remission; INTERFERONS; PROTEIN-tyrosine kinases; LYMPHOCYTES; PROTEINASES; LEUCOCYTE elastase; IMMUNOGENETICS
- Publication
PLoS ONE, 2010, Vol 5, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0011770