Cancer Immunology, Immunotherapy

, Volume 64, Issue 7, pp 791–804 | Cite as

Two distinct effector memory cell populations of WT1 (Wilms’ tumor gene 1)-specific cytotoxic T lymphocytes in acute myeloid leukemia patients

  • Yoshiki Nakae
  • Yoshihiro Oka
  • Fumihiro Fujiki
  • Soyoko Morimoto
  • Toshio Kamiya
  • Satoshi Takashima
  • Jun Nakata
  • Sumiyuki Nishida
  • Hiroko Nakajima
  • Naoki Hosen
  • Akihiro Tsuboi
  • Taiichi Kyo
  • Yusuke Oji
  • Kenji Mizuguchi
  • Atsushi Kumanogoh
  • Haruo SugiyamaEmail author
Original Article


Wilms’ tumor gene 1 (WT1) protein is a promising tumor-associated antigen for cancer immunotherapy. We have been performing WT1 peptide vaccination with good clinical responses in over 750 patients with leukemia or solid cancers. In this study, we generated single-cell gene-expression profiles of the effector memory (EM) subset of WT1-specific cytotoxic T lymphocytes (CTLs) in peripheral blood of nine acute myeloid leukemia patients treated with WT1 peptide vaccine, in order to discriminate responders (WT1 mRNA levels in peripheral blood decreased to undetectable levels, decreased but stayed at abnormal levels, were stable at undetectable levels, or remained unchanged from the initial abnormal levels more than 6 months after WT1 vaccination) from non-responders (leukemic blast cells and/or WT1 mRNA levels increased relative to the initial state within 6 months of WT1 vaccination) prior to WT1 vaccination. Cluster and principal component analyses performed using 83 genes did not discriminate between responders and non-responders prior to WT1 vaccination. However, these analyses revealed that EM subset of WT1-specific CTLs could be divided into two groups: the “activated” and “quiescent” states; in responders, EM subset of the CTLs shifted to the “quiescent” state, whereas in non-responders, those shifted to the “activated” state following WT1 vaccination. These results demonstrate for the first time the existence of two distinct EM states, each of which was characteristic of responders or non-responders, of WT1-specific CTLs in AML patients, and raises the possibility of using advanced gene-expression profile analysis to clearly discriminate between responders and non-responders prior to WT1 vaccination.


WT1 CTL Single-cell Gene-expression profiles 



Acute myeloid leukemia


Bone marrow


Cytotoxic T lymphocytes


Effector memory


Early relapse


Gene ontology


Hematological complete remission


Minimal residual disease


Peripheral blood


Peripheral blood mononuclear cells


Principal component analysis


First principal component


Second principal component


Pan-tumor-associated antigen


Wilms’ tumor gene 1



The authors thank the nursing teams for their care of the patients in this study and Ms. Tomoe Umeda for coordination of clinical research. This study was partially supported by the Japan Society for the Promotion of Science (JSPS) through grants for Scientific Research, and Grants-in-Aid for Young Scientists from the Ministry of Education, Science, Sports, Culture and Technology and the Ministry of Health, Labour and Welfare of Japan (Grant Nos. 24591164, 25830116, 25430186 and 25293079). The Department of Cancer Immunology is a department in collaboration with Otsuka Pharmaceutical Co., Ltd., and is supported with a grant from the company. The company had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Supplementary material

262_2015_1683_MOESM1_ESM.pdf (66 kb)
Supplementary material 1 (PDF 66 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Yoshiki Nakae
    • 1
  • Yoshihiro Oka
    • 1
    • 2
    • 3
  • Fumihiro Fujiki
    • 2
  • Soyoko Morimoto
    • 2
  • Toshio Kamiya
    • 8
  • Satoshi Takashima
    • 1
  • Jun Nakata
    • 4
  • Sumiyuki Nishida
    • 1
  • Hiroko Nakajima
    • 2
  • Naoki Hosen
    • 5
  • Akihiro Tsuboi
    • 4
  • Taiichi Kyo
    • 6
  • Yusuke Oji
    • 5
  • Kenji Mizuguchi
    • 7
  • Atsushi Kumanogoh
    • 1
    • 3
  • Haruo Sugiyama
    • 8
    Email author
  1. 1.Departments of Respiratory Medicine, Allergy and Rheumatic Diseases, Graduate School of MedicineOsaka UniversitySuitaJapan
  2. 2.Department of Cancer Immunology, Graduate School of MedicineOsaka UniversitySuitaJapan
  3. 3.Department of Immunopathology, Immunology Frontier Research Center (World Premier International Research Center)Osaka UniversitySuitaJapan
  4. 4.Department of Cancer Immunotherapy, Graduate School of MedicineOsaka UniversitySuitaJapan
  5. 5.Department of Cancer Stem Cell Biology, Graduate School of MedicineOsaka UniversitySuitaJapan
  6. 6.Department of HematologyHiroshima Red Cross and Atomic Bomb Survivor HospitalHiroshima-CityJapan
  7. 7.National Institute of Biomedical InnovationIbarakiJapan
  8. 8.Department of Functional Diagnostic Science, Graduate School of MedicineOsaka UniversitySuitaJapan

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