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

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-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.

• 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
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 70 Issue 1 Pg. 253-263 (Jan 2021) ISSN: 1432-0851 [Electronic] Germany
• PMID: 32696072 (Publication Type: Journal Article)

Chemical References

• Antigens, Neoplasm
• CD5 Antigens
• Cancer Vaccines
• Peptides
• Vaccines, Subunit
• WT1 Proteins
• WT1 protein, human

Topics

• Antigens, Neoplasm (immunology)
• CD5 Antigens (immunology)
• Cancer Vaccines (immunology)
• Cell Death (immunology)
• Cell Proliferation (physiology)
• Cells, Cultured
• Humans
• Leukocytes, Mononuclear (immunology)
• Neoplasm Recurrence, Local (immunology)
• Peptides (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)
• Vaccination (methods)
• Vaccines, Subunit (immunology)
• WT1 Proteins (immunology)