The MDM2 inhibitor Nutlin-3 modulates dendritic cell-induced T cell proliferation
The MDM2 inhibitor Nutlin-3 modulates dendritic cell-induced T cell proliferation
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DOI：
10.1016/j.humimm.2012.01.018
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发表时间：
2012-04-01
期刊：
影响因子：
2.7
通讯作者：
Zauli, Giorgio
中科院分区：
文献类型：
--
作者：
Gasparini, Chiara;Tommasini, Alberto;Zauli, Giorgio
Nutlin-3是一种MDM 2/p53相互作用的小分子抑制剂，基于其稳定和激活p53转录因子途径的能力，最近已被认为是一种有前途的肿瘤治疗工具。由于Nutlin-3显示出非细胞自主的肿瘤抑制活性，我们想研究其对树突状细胞功能的影响，因为这些细胞在调节免疫应答中起着重要作用。我们发现，Nutlin-3单独轻微影响主要组织相容性复合物和共刺激分子的水平，并显着促进树突状细胞刺激混合淋巴细胞反应中的T细胞的能力。综上所述，我们的研究结果表明，Nutlin-3调节树突状细胞功能的能力，因此淋巴细胞增殖可能是Nutlin-3发挥其非细胞自主肿瘤抑制功能的另一个重要机制。(C)2012年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版All rights reserved.
Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, has been recently taken into consideration as a promising therapeutic tool for tumor treatment based on its ability to stabilize and activate the p53 transcription factor pathway. Since Nutlin-3 displays non cell-autonomous tumor-suppressor activities, we wanted to investigate its effect on dendritic cell functions, given the central role of these cells in the modulation of the immune response. We found that Nutlin-3 alone slightly affected the levels of major histocompatibility complex and costimulatory molecules and significantly promoted the ability of dendritic cells to stimulate T cells in the mixed lymphocyte reaction. Taken together, our findings suggest that the ability of Nutlin-3 to modulate dendritic cell functions and therefore lymphocyte proliferation might represent an additional important mechanism by which Nutlin-3 exerts its non cell-autonomous tumor-suppression function. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.