Identification of two distinct populations of WT1-specific cytotoxic T lymphocytes in co-vaccination of WT1 killer and helper peptides
| Autor: | Naoya Hashimoto, Kana Hasegawa, Shinji Sogo, Haruo Sugiyama, Yoshihiro Oka, Yusuke Oji, Naoki Hosen, Fumihiro Fujiki, Jun Nakata, Soyoko Morimoto, Akihiro Tsuboi, Hiroko Nakajima, Sumiyuki Nishida, Miki Inatome |
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| Rok vydání: | 2020 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Cancer Research education.field_of_study urogenital system Helper T lymphocyte T cell fungi Immunology Population Human leukocyte antigen Biology urologic and male genital diseases female genital diseases and pregnancy complications CTL medicine.anatomical_structure Immune system Oncology medicine Peptide vaccine Immunology and Allergy Cytotoxic T cell education |
| Zdroj: | Cancer Immunology, Immunotherapy. 70:253-263 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-020-02675-9 |
| Popis: | 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-tetramerlow WT1-TCRlow CD5low and WT1-tetramerhigh WT1-TCRhigh CD5high 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. |
| Databáze: | OpenAIRE |
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