Enhancement of adoptive T cell transfer with single low dose pretreatment of doxorubicin or paclitaxel in mice

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Title:	Enhancement of adoptive T cell transfer with single low dose pretreatment of doxorubicin or paclitaxel in mice
Authors:	許斐婷;Hsu, Fei-Ting;Chen, Tzu-Chun;Chuang, Hui-Yen;Chang, Ya-Fang;Hwang, Jeng-Jong
Contributors:	生醫理工學院生命科學系
Keywords:	Adoptive Transfer - methods;Animals;CD8-Positive T-Lymphocytes - drug effects;CD8-Positive T-Lymphocytes - immunology;CD8-Positive T-Lymphocytes - metabolism;CD8-Positive T-Lymphocytes - transplantation;Coculture Techniques;Dose-Response Relationship, Drug;Doxorubicin - pharmacology;Genes, Reporter;Granzymes - genetics;HEK293 Cells;Humans;Immunosuppressive Agents - pharmacology;Jurkat Cells;Luciferases, Firefly - biosynthesis;Luciferases, Firefly - genetics;Lymphocyte Activation - drug effects;Lymphocytes, Tumor-Infiltrating - immunology;Lymphocytes, Tumor-Infiltrating - metabolism;Lymphoma - genetics;Lymphoma - immunology;Lymphoma - metabolism;Lymphoma - therapy;Male;Mice, Inbred C57BL;NF-kappa B - antagonists & inhibitors;NF-kappa B - immunology;NF-kappa B - metabolism;Paclitaxel - pharmacology;Promoter Regions, Genetic;Recombinant Fusion Proteins - biosynthesis;Recombinant Fusion Proteins - genetics;Research Paper: Immunology;Signal Transduction;T-Lymphocytes, Regulatory - immunology;T-Lymphocytes, Regulatory - metabolism;Time Factors;Transfection;Tumor Escape;Tumor Microenvironment
Date:	2015-01-01
Issue Date:	2026-04-23 11:12:35 (UTC+8)
Publisher:	Impact Journals LLC;United States: Impact Journals LLC
Abstract:	摘要： Ex vivo expansion of CD8+ T-cells has been a hindrance for the success of adoptive T cell transfer in clinic. Currently, preconditioning with chemotherapy is used to modulate the patient immunity before ACT, however, the tumor microenvironment beneficial for transferring T cells may also be damaged. Here preconditioning with single low dose of doxorubicin or paclitaxel combined with fewer CD8+ T-cells was investigated to verify whether the same therapeutic efficacy of ACT could be achieved. An E.G7/OT1 animal model that involved adoptive transfer of OVA-specific CD8+ T-cells transduced with a granzyme B promoter-driven firefly luciferase and tomato fluorescent fusion reporter gene was used to evaluate this strategy. The result showed that CD8+ T-cells were activated and sustained longer in mice pretreated with one low-dose Dox or Tax. Enhanced therapeutic efficacy was found in Dox or Tax combined with 2x106 CD8+ T-cells and achieved the same level of tumor growth inhibition as that of 5x106 CD8+ T-cells group. Notably, reduced numbers of Tregs and myeloid derived suppressor cells were shown in combination groups. By contrast, the number of tumor-infiltrating cytotoxic T lymphocytes and IL-12 were increased. The NF-κB activity and immunosuppressive factors such as TGF-β, IDO, CCL2, VEGF, CCL22, COX-2 and IL-10 were suppressed. This study demonstrates that preconditioning with single low dose Dox or Tax and combined with two fifth of the original CD8+ T-cells could improve the tumor microenvironment via suppression of NF-κB and its related immunosuppressors, and activate more CD8+ T-cells which also stay longer. 其他題名： Oncotarget 出版者： United States: Impact Journals LLC 出版日期： 2015-12-29 出處： Oncotarget, 2015-12, Vol.6 (42), p.44134-44150 版權： Copyright: © 2015 Hsu et al. 2015 識別號： ISSN: 1949-2553 識別號： EISSN: 1949-2553 識別號： DOI: 10.18632/oncotarget.6628 識別號： PMID: 26683520
Appears in Collections:	[Department of Life Science] journal & Dissertation

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