Signaling pathways induced by a tumor-derived vaccine in antigen presenting cells.
Signaling pathways induced by a tumor-derived vaccine in antigen presenting cells.
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DOI：
10.1016/j.imbio.2009.09.006
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发表时间：
2010-07
期刊：
影响因子：
2.8
通讯作者：
Katsanis, Emmanuel
中科院分区：
文献类型：
--
作者：
Cantrell, Jessica;Larmonier, Claire;Janikashvili, Nona;Bustamante, Sara;Fraszczak, Jennifer;Herrell, Amanda;Lundeen, Tamara;LaCasse, Collin J.;Situ, Elaine;Larmonier, Nicolas;Katsanis, Emmanuel
我们以前曾报道过一种富含伴侣蛋白的细胞裂解液（CRCL）疫苗的抗肿瘤潜力。在许多小鼠肿瘤模型中，用肿瘤产生的CRCL免疫可引起特异性T和NK细胞依赖的免疫反应，从而产生保护性免疫。CRCL既是肿瘤抗原的来源，也是导致树突状细胞活化的危险信号。在人体中，肿瘤来源的CRCL诱导树突状细胞活化，体外加载CRCL的树突状细胞促进细胞毒性T淋巴细胞的产生。目前的研究旨在确定抗原呈递细胞中由CRCL触发的信号事件和修饰。我们的研究结果表明，肿瘤来源的CRCL不仅促进树突状细胞的活化，而且显著促进巨噬细胞的功能，因此巨噬细胞成为该疫苗的主要靶点。这两种细胞类型的激活都与MAP激酶通路的诱导、STAT1、STAT5和AKT的磷酸化以及转录因子NF-κB的激活有关。因此，这些结果为了解基于crcl的疫苗对抗原提呈细胞发挥佐剂作用的机制提供了重要的见解。
We have previously reported on the anti-tumoral potential of a chaperone-rich cell lysate (CRCL) vaccine. Immunization with CRCL generated from tumors elicits specific T and NK cell-dependent immune responses leading to protective immunity in numerous mouse tumor models. CRCL provides both a source of tumor antigens and danger signals leading to dendritic cell activation. In humans, tumor-derived CRCL induces dendritic cell activation and CRCL-loaded dendritic cells promote the generation of cytotoxic T lymphocytes in vitro. The current study was designed to identify the signaling events and modifications triggered by CRCL in antigen presenting cells. Our results indicate that tumor-derived CRCL not only promotes the activation of dendritic cells, but also significantly fosters the function of macrophages that thus appear as major targets of this vaccine. Activation of both cell types is associated with the induction of the MAP kinase pathway, the phosphorylation of STAT1, STAT5 and AKT and with transcription factor NF-κB activation in vitro and in vivo. These results thus provide important insights into the mechanisms by which CRCL-based vaccines exert their adjuvant effects on antigen presenting cells.
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影响因子：
5.8
作者：
Graner, MW;Yi, Z;Katsanis, E
通讯作者：
Katsanis, E
影响因子：
7.2
作者：
Larmonier, Nicolas;Merino, Delphine;Bonnotte, Bernard
通讯作者：
Bonnotte, Bernard
影响因子：
32.4
作者：
Basu, S;Binder, RJ;Srivastava, PK
通讯作者：
Srivastava, PK
影响因子：
4.8
作者：
Gao, BC;Tsan, MF
通讯作者：
Tsan, MF
影响因子：
30.5
作者：
Binder, RJ;Han, DK;Srivastava, PK
通讯作者：
Srivastava, PK