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Impact of mature dendritic cells pulsed with a novel WT1 helper peptide on the induction of HLA­A2­restricted WT1­reactive CD8+ T cells.
Kan, Shin; Bito, Tsuuse; Shimabuku, Masamori; Taguchi, Junichi; Ohkusa, Toshifumi; Shimodaira, Shigetaka; Sugiyama, Haruo; Koido, Shigeo.
Afiliación
  • Kan S; Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277­8567, Japan.
  • Bito T; Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277­8567, Japan.
  • Shimabuku M; Tokyo Midtown Center for Advanced Medical Science and Technology, Tokyo 107­6206, Japan.
  • Taguchi J; Tokyo Midtown Center for Advanced Medical Science and Technology, Tokyo 107­6206, Japan.
  • Ohkusa T; Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277­8567, Japan.
  • Shimodaira S; Department of Regenerative Medicine, Kanazawa Medical University, Ishikawa 920­0293, Japan.
  • Sugiyama H; Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka 565­0871, Japan.
  • Koido S; Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277­8567, Japan.
Int J Oncol ; 57(4): 1047-1056, 2020 10.
Article en En | MEDLINE | ID: mdl-32945369
The proliferation and activation of CD4+ T helper 1 (Th1) cells and CD8+ cytotoxic T lymphocytes (CTLs) that produce interferon­Î³ (IFN­Î³) is an essential action of effective cancer vaccines. Recently, a novel Wilms' tumor 1 (WT1) helper peptide (WT1 HP34­51; amino acid sequence, WAPVLDFAPPGASAYGSL) applicable for various human leukocyte antigen (HLA) subtypes (HLA­DR, HLA­DP and HLA­DQ) was reported to increase peptide immunogenicity; however, the function of WT1 HP34­51 remains unclear. In the present study, mature dendritic cells (mDCs) pulsed with WT1 HP34­51 (mDC/WT1 HP34­51) activated not only WT1­specific CD4+ T cells but also CD8+ T cells that produced IFN­Î³ following stimulation with immature dendritic cells (imDCs) pulsed with WT1 killer peptide (imDC/WT1 KP37­45) in an HLA­A*02:01­ or HLA­A*02:06­restricted manner. Furthermore, the activated WT1­reactive CD4+ Th1 cells were predominantly effector memory (EM) T cells. In 5 of 12 (41.7%) patients with cancer carrying the HLA­A*02:01 or HLA­A*02:06 allele, WT1­reactive CD8+ T cells stimulated with mDC/WT1 HP34­51 enhanced their levels of WT1 KP37­45­specific IFN­Î³ production, with an increase >10%. Simultaneous activation of CD4+ and CD8+ T cells occurred more often when stimulation with mDC/WT1 HP34­51 was combined with imDC/WT1 KP37­45 restimulation. These results indicated that the novel mDC/WT1 HP34­51 combination induced responses by WT1­specific EM CD4+ Th1 cells and HLA­A*02:01­ or HLA­A*02:06­restricted CD8+ CTLs, suggesting its potential as a WT1­targeting cancer vaccine.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Células Dendríticas / Antígeno HLA-A2 / Tumor de Wilms / Linfocitos T CD8-positivos / Proteínas WT1 / Neoplasias Renales Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Oncol Asunto de la revista: NEOPLASIAS Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Grecia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Células Dendríticas / Antígeno HLA-A2 / Tumor de Wilms / Linfocitos T CD8-positivos / Proteínas WT1 / Neoplasias Renales Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Oncol Asunto de la revista: NEOPLASIAS Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Grecia