PMID- 32945369 OWN - NLM STAT- MEDLINE DCOM- 20210714 LR - 20210908 IS - 1791-2423 (Electronic) IS - 1019-6439 (Linking) VI - 57 IP - 4 DP - 2020 Oct TI - Impact of mature dendritic cells pulsed with a novel WT1 helper peptide on the induction of HLA‑A2‑restricted WT1‑reactive CD8+ T cells. PG - 1047-1056 LID - 10.3892/ijo.2020.5110 [doi] AB - The proliferation and activation of CD4+ T helper 1 (Th1) cells and CD8+ cytotoxic T lymphocytes (CTLs) that produce interferon‑gamma (IFN‑gamma) 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‑gamma 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‑gamma 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. FAU - Kan, Shin AU - Kan S AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277‑8567, Japan. FAU - Bito, Tsuuse AU - Bito T AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277‑8567, Japan. FAU - Shimabuku, Masamori AU - Shimabuku M AD - Tokyo Midtown Center for Advanced Medical Science and Technology, Tokyo 107‑6206, Japan. FAU - Taguchi, Junichi AU - Taguchi J AD - Tokyo Midtown Center for Advanced Medical Science and Technology, Tokyo 107‑6206, Japan. FAU - Ohkusa, Toshifumi AU - Ohkusa T AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277‑8567, Japan. FAU - Shimodaira, Shigetaka AU - Shimodaira S AD - Department of Regenerative Medicine, Kanazawa Medical University, Ishikawa 920‑0293, Japan. FAU - Sugiyama, Haruo AU - Sugiyama H AD - Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka 565‑0871, Japan. FAU - Koido, Shigeo AU - Koido S AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277‑8567, Japan. LA - eng PT - Journal Article DEP - 20200814 PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (HLA-A2 Antigen) RN - 0 (Peptide Fragments) RN - 0 (WT1 Proteins) RN - 0 (WT1 protein, human) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - Cells, Cultured MH - Dendritic Cells/drug effects/*immunology/transplantation MH - Female MH - HLA-A2 Antigen/*immunology MH - Humans MH - Immunotherapy, Adoptive/methods MH - Kidney Neoplasms/blood/immunology/*therapy MH - Leukocytes, Mononuclear MH - Male MH - Middle Aged MH - Peptide Fragments/*pharmacology MH - Th1 Cells/immunology MH - WT1 Proteins/*immunology MH - Wilms Tumor/blood/immunology/*therapy OTO - NOTNLM OT - dendritic cell OT - Wilms' tumor 1 OT - helper peptide OT - cytotoxic T lymphocytes OT - interferon-gamma EDAT- 2020/09/19 06:00 MHDA- 2021/07/15 06:00 CRDT- 2020/09/18 08:43 PHST- 2020/03/15 00:00 [received] PHST- 2020/07/31 00:00 [accepted] PHST- 2020/09/19 06:00 [pubmed] PHST- 2021/07/15 06:00 [medline] PHST- 2020/09/18 08:43 [entrez] AID - 10.3892/ijo.2020.5110 [doi] PST - ppublish SO - Int J Oncol. 2020 Oct;57(4):1047-1056. doi: 10.3892/ijo.2020.5110. Epub 2020 Aug 14.