論文

査読有り
2017年4月

Graft-versus-leukemia effect with a WT1-specific T-cell response induced by azacitidine and donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation

CYTOTHERAPY
  • Tatsunori Ishikawa
  • ,
  • Nobuharu Fujii
  • ,
  • Masahide Imada
  • ,
  • Michinori Aoe
  • ,
  • Yusuke Meguri
  • ,
  • Tomoko Inomata
  • ,
  • Hiromi Nakashimai
  • ,
  • Keiko Fujii
  • ,
  • Shohei Yoshida
  • ,
  • Hisakazu Nishimori
  • ,
  • Ken-Ichi Matsuoka
  • ,
  • Eisei Kondo
  • ,
  • Yoshinobu Maeda
  • ,
  • Mitsune Tanimoto

19
4
開始ページ
514
終了ページ
520
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jcyt.2016.12.007
出版者・発行元
ELSEVIER SCI LTD

Background. Azacitidine (Aza) and donor lymphocyte infusion (DLI) therapy has recently been reported as an effective salvage therapy for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite the high response rate and relatively long period of remission, most patients relapse again. The immunologic mechanism of the response and limited efficacy remain unknown. Case Report. Aza + DLI therapy was performed for a patient with therapy-related MDS (t-MDS), who had relapsed after allogeneic peripheral blood stem cell transplantation. We observed a powerful graft versus-leukemia (GVL) effect accompanied by an evident Wilms tumor antigen 1 (WT1)-specific CD8 T-cell response. Remission continued for 15 months, but finally the patient relapsed. The kinetics of the WT1-specific CD8 T cells were inversely associated with WT1 messenger RNA (mRNA), suggesting a WT1-driven GVL effect. Discussion. A difference of T-cell phenotype between the whole T cells and the WT1-specific CD8 T cells was observed. It is of note that the memory phenotype of the WT1-specific T cell was limited and decreased early. The immunoescape mechanism was partly supported by loss of the memory phenotype due to failure of expansion and differentiation. Conclusion. Our data suggested that a WT1-specific T-cell response at least partly contributes to the GVL effect induced by Aza + DLI. A strategy for maximizing and maintaining the memory phenotype of the CTL may be required for durable remission.

Web of Science ® 被引用回数 : 11

リンク情報
DOI
https://doi.org/10.1016/j.jcyt.2016.12.007
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000396968100006&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-85010918142&partnerID=MN8TOARS
URL
http://orcid.org/0000-0003-0995-9405

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