Short‐term cultured autologous peripheral blood mononuclear cells as a potential immunogen to activate Tax‐specific CTL response in adult T‐cell leukemia patients
| العنوان: | Short‐term cultured autologous peripheral blood mononuclear cells as a potential immunogen to activate Tax‐specific CTL response in adult T‐cell leukemia patients |
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| المؤلفون: | Nobuyo Kondo, Undrakh Ganbaatar, Miku Ishizawa, Takao Masuda, Natsuko Takatsuka, Kuniko Katagiri, Mari Kannagi, Takeru Yoneda, Atsuhiko Hasegawa, Atae Utsunomiya |
| المصدر: | Cancer Science |
| بيانات النشر: | John Wiley and Sons Inc., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Immunogen, Time Factors, medicine.medical_treatment, Mitomycin, Tax, Cell Culture Techniques, Human leukocyte antigen, Peripheral blood mononuclear cell, Inflammation and Virology, Cancer Vaccines, Transplantation, Autologous, 03 medical and health sciences, 0302 clinical medicine, Cross-Priming, Antigen, Cell Line, Tumor, HLA-A2 Antigen, Medicine, Humans, Leukemia-Lymphoma, Adult T-Cell, Antigen-presenting cell, Antigens, Viral, CD86, Human T-lymphotropic virus 1, business.industry, hemic and immune systems, General Medicine, Immunotherapy, Original Articles, Gene Products, tax, HTLV-I Infections, Coculture Techniques, Histone Deacetylase Inhibitors, CTL, 030104 developmental biology, Oncology, ATL, 030220 oncology & carcinogenesis, Immunology, tumor vaccine, Leukocytes, Mononuclear, Original Article, HTLV‐1, business, T-Lymphocytes, Cytotoxic |
| الوصف: | Activation of CD8+ Tax‐specific CTL is a new therapeutic concept for adult T‐cell leukemia (ATL) caused by HTLV‐1. A recent clinical study of the dendritic cell vaccine pulsed with Tax peptides corresponding to CTL epitopes showed promising outcomes in ATL patients possessing limited human leukocyte antigen (HLA) alleles. In this study, we aimed to develop another immunotherapy to activate Tax‐specific CTL without HLA limitation by using patients’ own HTLV‐1‐infected cells as a vaccine. To examine the potential of HTLV‐1‐infected T‐cells to activate CTL via antigen presenting cells, we established a unique co–culture system. We demonstrated that mitomycin C‐treated HLA‐A2‐negative HTLV‐1‐infected T‐cell lines or short‐term cultured peripheral blood mononuclear cells (PBMC) derived from ATL patients induced cross–presentation of Tax antigen in co–cultured HLA‐A2‐positive antigen presenting cells, resulting in activation of HLA‐A2‐restricted CD8+ Tax‐specific CTL. This effect was not inhibited by a reverse transcriptase inhibitor. IL‐12 production and CD86 expression were also induced in antigen presenting cells co–cultured with HTLV‐1‐infected cells at various levels, which were improved by pre–treatment of the infected cells with histone deacetylase inhibitors. Furthermore, monocyte‐derived dendritic cells induced from PBMC of a chronic ATL patient produced IL‐12 and expressed enhanced levels of CD86 when co–cultured with autologous lymphocytes that had been isolated from the same PBMC and cultured for several days. These findings suggest that short‐term cultured autologous PBMC from ATL patients could potentially serve as a vaccine to evoke Tax‐specific CTL responses. Repression of viral antigen expression in vivo is one of the strategies of HTLV‐1 persistence, whereas viral expression is inducible in vitro. The present study indicates that short‐term cultured ATL cells express Tax and induce Tax cross–presentation, costimulatory molecule expression, and IL‐12 production in the antigen‐presenting cells, providing evidence that the short‐term cultured ATL cells may potentially act as a therapeutic vaccine to induce Tax‐specific CTL. |
| اللغة: | English |
| تدمد: | 1349-7006 1347-9032 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3fd6f0ab4f5307156fd95a5bb91e7e62 http://europepmc.org/articles/PMC7935807 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3fd6f0ab4f5307156fd95a5bb91e7e62 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 13479032 |
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