4-1BB Protects Dendritic Cells from Prostate Cancer-Induced Apoptosis
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RESEARCH
4-1BB Protects Dendritic Cells from Prostate Cancer-Induced Apoptosis Kuang Youlin & Zhang Jianwei & Gou Xin & Zhang Li & Weng Xiaodong & Liu Xiuheng & Zhu Hengchen & Chen Zhiyuan
Received: 30 August 2011 / Accepted: 15 August 2012 / Published online: 16 October 2012 # Arányi Lajos Foundation 2012
Abstract It has been shown that human prostate cancer (PCa) cells induced apoptotic death of the most potent antigen-presenting cells, dendritic cells (DCs), which are responsible for the induction of specific antitumor immune responses. Here, we investigated the function of 4-1BB on protecting DCs from prostate cancer-induced apoptosis with an agonistic mAb to 4-1BB. RM-1 cells and DCs were coincubated for 48 h and DC apoptosis was assessed by Annexin Vassay. TNF-α and IL-12 production were assessed by enzyme-linked immunosorbent assay (ELISA) and Bcl-2 and Bcl-xL on DCs were analyzed by Western blot. We have shown that co-incubation of RM-1 cells with DCs is accompanied by an increased level of DCs apoptosis. Triggering 4-1BB on DCs resulted in increased resistance of DCs to RM-1 cells-induced apoptosis, which was owing to the up-regulated expression of Bcl-2 and Bcl-xL, and increased secretion of TNF-αand IL-12. These results Kuang Youlin, Zhang Jianwei contributed equally to this work and should be considered co-first authors. K. Youlin Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China Z. Jianwei Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China G. Xin (*) Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China e-mail: [email protected] Z. Li : W. Xiaodong : L. Xiuheng : Z. Hengchen : C. Zhiyuan Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
demonstrate that triggering 4-1BB on DCs could increased resistance of DCs to PCa-induced apoptosis. Keywords Dendritic cells . Co-stimulatory molecules . 4-1BB . Prostate cancer
Introduction Prostate cancer (PCa) is the most frequently diagnosed cancer in old men and also the second leading cause of male cancer death in the Western countries [1]. In addition, the incidence and mortality of carcinoma of prostate are increasing in China. Treatment of advanced prostate cancer is still far from satisfactory, especially when the tumor reaches the hormone-resistant state. In the past decade, a wide array of immunotherapeutic strategies has been developed for prostate cancer and successfully tested in animals and humans. Among these, the dendritic cells (DCs)-based vaccine has been one of the treatment modalities most extensively studied in a variety of preclinical models [2], and clinical trials [3, 4]. DCs, which are the most potent APCs, are known to be deficient in number and functional activity in patients with cancer [5]. Elimination of DCs from the tumor environment significantly diminishes the initiation of specific immunologic responses. However, recent research demonstrated that human prostate
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