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01.07.2015 | Original Article

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

verfasst von: 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 Sugiyama

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2015

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Abstract

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.

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Titel: Two distinct effector memory cell populations of WT1 (Wilms’ tumor gene 1)-specific cytotoxic T lymphocytes in acute myeloid leukemia patients
verfasst von: 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 Sugiyama
Publikationsdatum: 01.07.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 7/2015
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-015-1683-7

Springer Medizin

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

Abstract

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Springer Medizin

Abstract

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