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01-01-2021 | Vaccination | Original Article

Identification of two distinct populations of WT1-specific cytotoxic T lymphocytes in co-vaccination of WT1 killer and helper peptides

Authors: Fumihiro Fujiki, Akihiro Tsuboi, Soyoko Morimoto, Naoya Hashimoto, Miki Inatome, Hiroko Nakajima, Jun Nakata, Sumiyuki Nishida, Kana Hasegawa, Naoki Hosen, Yoshihiro Oka, Yusuke Oji, Shinji Sogo, Haruo Sugiyama

Published in: Cancer Immunology, Immunotherapy | Issue 1/2021

Abstract

Simultaneous induction of tumor antigen-specific cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs) is required for an optimal anti-tumor immune response. WT1₃₃₂, a 16-mer WT1-derived helper peptide, induce HTLs in an HLA class II-restricted manner and enhance the induction of WT1-specific CTLs in vitro. However, in vivo immune reaction to WT1₃₃₂ vaccination in tumor-bearing patients remained unclear. Here, a striking difference in WT1-specific T cell responses was shown between WT1 CTL + WT1 helper peptide and WT1 CTL peptide vaccines in patients with recurrent glioma. WT1-specific CTLs were more strongly induced in the patients who were immunized with WT1 CTL + WT1 helper peptide vaccine, compared to those who were immunized with WT1 CTL vaccine alone. Importantly, a clear correlation was demonstrated between WT1-specific CTL and WT1₃₃₂-specific HTL responses. Interestingly, two novel distinct populations of WT1-tetramer^low WT1-TCR^low CD5^low and WT1-tetramer^high WT1-TCR^high CD5^high CTLs were dominantly detected in WT1 CTL + WT1 helper peptide vaccine. Although natural WT1 peptide-reactive CTLs in the latter population were evidently less than those in the former population, the latter population showed natural WT1 peptide-specific proliferation capacity comparable to the former population, suggesting that the latter population highly expressing CD5, a marker of resistance to activation-induced cell death, should strongly expand and persist for a long time in patients. These results demonstrated the advantage of WT1 helper peptide vaccine for the enhancement of WT1-specific CTL induction by WT1 CTL peptide vaccine.

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Title: Identification of two distinct populations of WT1-specific cytotoxic T lymphocytes in co-vaccination of WT1 killer and helper peptides
Authors: Fumihiro Fujiki
Akihiro Tsuboi
Soyoko Morimoto
Naoya Hashimoto
Miki Inatome
Hiroko Nakajima
Jun Nakata
Sumiyuki Nishida
Kana Hasegawa
Naoki Hosen
Yoshihiro Oka
Yusuke Oji
Shinji Sogo
Haruo Sugiyama
Publication date: 01-01-2021
Publisher: Springer Berlin Heidelberg
Keywords: Vaccination
Cytokines
Published in: Cancer Immunology, Immunotherapy / Issue 1/2021
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02675-9

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