Impact of mature dendritic cells pulsed with a novel WT1 helper peptide on the induction of HLA‑A2‑restricted WT1‑reactive CD8+ T cells

Kan,Shin; Bito,Tsuuse; Shimabuku,Masamori; Taguchi,Junichi; Ohkusa,Toshifumi; Shimodaira,Shigetaka; Sugiyama,Haruo; Koido,Shigeo

doi:10.3892/ijo.2020.5110

Impact of mature dendritic cells pulsed with a novel WT1 helper peptide on the induction of HLA‑A2‑restricted WT1‑reactive CD8+ T cells

Authors:
- Shin Kan
- Tsuuse Bito
- Masamori Shimabuku
- Junichi Taguchi
- Toshifumi Ohkusa
- Shigetaka Shimodaira
- Haruo Sugiyama
- Shigeo Koido
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Affiliations: Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277‑8567, Japan, Tokyo Midtown Center for Advanced Medical Science and Technology, Tokyo 107‑6206, Japan, Department of Regenerative Medicine, Kanazawa Medical University, Ishikawa 920‑0293, Japan, Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka 565‑0871, Japan
Published online on: August 14, 2020 https://doi.org/10.3892/ijo.2020.5110
Pages: 1047-1056

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Abstract

The proliferation and activation of CD4+ T helper 1 (Th1) cells and CD8+ cytotoxic T lymphocytes (CTLs) that produce interferon‑γ (IFN‑γ) is an essential action of effective cancer vaccines. Recently, a novel Wilms' tumor 1 (WT1) helper peptide (WT1 HP34‑51; amino acid sequence, WAPVLDFAPPGASAYGSL) applicable for various human leukocyte antigen (HLA) subtypes (HLA‑DR, HLA‑DP and HLA‑DQ) was reported to increase peptide immunogenicity; however, the function of WT1 HP34‑51 remains unclear. In the present study, mature dendritic cells (mDCs) pulsed with WT1 HP34‑51 (mDC/WT1 HP34‑51) activated not only WT1‑specific CD4+ T cells but also CD8+ T cells that produced IFN‑γ following stimulation with immature dendritic cells (imDCs) pulsed with WT1 killer peptide (imDC/WT1 KP37‑45) in an HLA‑A*02:01‑ or HLA‑A*02:06‑restricted manner. Furthermore, the activated WT1‑reactive CD4+ Th1 cells were predominantly effector memory (EM) T cells. In 5 of 12 (41.7%) patients with cancer carrying the HLA‑A*02:01 or HLA‑A*02:06 allele, WT1‑reactive CD8+ T cells stimulated with mDC/WT1 HP34‑51 enhanced their levels of WT1 KP37‑45‑specific IFN‑γ production, with an increase >10%. Simultaneous activation of CD4+ and CD8+ T cells occurred more often when stimulation with mDC/WT1 HP34‑51 was combined with imDC/WT1 KP37‑45 restimulation. These results indicated that the novel mDC/WT1 HP34‑51 combination induced responses by WT1‑specific EM CD4+ Th1 cells and HLA‑A*02:01‑ or HLA‑A*02:06‑restricted CD8+ CTLs, suggesting its potential as a WT1‑targeting cancer vaccine.

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