Induction of T-cell responses against cutaneous T-cell lymphomas ex vivo by autologous dendritic cells transfected with amplified tumor mRNA.
Induction of T-cell responses against cutaneous T-cell lymphomas ex vivo by autologous dendritic cells transfected with amplified tumor mRNA.
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通过转染扩增的肿瘤 mRNA 的自体树突状细胞，在体外诱导针对皮肤 T 细胞淋巴瘤的 T 细胞反应。
DOI：
10.1038/jid.2008.125
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Duvic,Madeleine
中科院分区：
文献类型：
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作者：
Ni,Xiao;Richmond,HeatherM;Liao,XingshengM;Decker,WilliamK;Shiue,LisaH;Shpall,ElizabethJ;Duvic,Madeleine
Szary综合征（SzS）是皮肤T细胞淋巴瘤的白血病变体，是无法治愈的。肿瘤mRNA转染的树突状细胞（Dendritic cells，DCs）可刺激某些肿瘤患者产生抗肿瘤免疫。在这项研究中，我们确定了来自Sézary细胞的mRNA是否可以用于负载DC和刺激抗肿瘤免疫。从10例SzS患者的外周血单核细胞中产生自体DC。从Sézary细胞中提取总RNA，并通过T7体外转录进行扩增。ELISA POT法检测RNA转染的DC诱导产生抗肿瘤IFN-γ和颗粒酶B（GrB）的细胞毒性T淋巴细胞（CTL）。我们发现IFN-γ是由来自SzS的单核细胞衍生的DC产生IL-12 p70所必需的。致癌转录因子Twist和酪氨酸激酶受体EphA 4在来自Sézary细胞的总RNA和成对扩增的mRNA中表达。RNA转染的DC在10名受试者中的7名中诱导产生抗肿瘤IFN-γ的CTL，在9名受试者中的6名中诱导产生GrB的CTL。CD 3 + CD 8 + T细胞和CD 4 + CD 25 + T细胞均扩增，而不诱导调节性T细胞。这些数据支持将肿瘤mRNA用于疫苗策略的概念，该策略需要少量肿瘤细胞而不需要SzS患者的特异性抗原。
Sézary syndrome (SzS), the leukemic variant of cutaneous T-cell lymphomas, is incurable. Dendritic cells (DCs) transfected with tumor mRNA can stimulate antitumor immunity in certain cancer patients. In this study, we determined whether mRNAs from Sézary cells could be used for loading DCs and stimulating antitumor immunity. Autologous DCs were generated from monocytes of the peripheral blood from 10 patients with SzS. Total RNA was extracted from Sézary cells and amplified by T7in vitrotranscription. The induction of antitumor IFN-γ and granzyme B (GrB)-producing cytotoxic T lymphocytes (CTL) by RNA-transfected DCs was determined by ELISPOT assays. We found that IFN-γ was required for IL-12p70 production by monocyte-derived DCs from SzS. The oncogenic transcription factor Twist and the tyrosine kinase receptor EphA4 were expressed in total RNA from Sézary cells and the paired amplified mRNAs. RNA-transfected DCs induced antitumor IFN-γ-producing CTLs in 7 of 10 subjects and GrB-producing CTLs in 6 of 9 subjects. Both CD3+CD8+ T cells and CD4+CD25+ T cells were expanded without induction of regulatory T cells. These data support the concept of using tumor mRNA for a vaccine strategy that requires small amounts of tumor cells without need for specific antigens in patients with SzS.