Zeng Yi, Chen Xinchun, Larmonier Nicolas, Larmonier Claire, Li Gang, Sepassi Marjan, Marron Marilyn, Andreansky Samita, Katsanis Emmanuel
Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ 85724-5073, USA.
Int J Cancer. 2006 Dec 1;119(11):2624-31. doi: 10.1002/ijc.22150.
Tumor derived chaperone-rich cell lysate (CRCL) when isolated from tumor tissues is a potent vaccine that contains at least 4 of the highly immunogenic heat shock proteins (HSP) such as HSP70, HSP90, glucose related protein 94 and calreticulin. We have previously documented that CRCL provides both a source of tumor antigens and danger signals triggering dendritic cell (DC) activation. Immunization with tumor derived CRCL elicits tumor-specific T cell responses leading to tumor regression. In the current study, we further dissect the mechanisms by which CRCL simulates the immune system, and demonstrate that natural killer (NK) cells are required for effective antitumor effects to take place. Our results illustrate that CRCL directly stimulates proinflammatory cytokine and chemokine production by NK cells, which may lead to activation and recruitment of macrophages at the tumor site. Thus, this report provides further insight into the function of CRCL as an immunostimulant against cancer.
从肿瘤组织中分离出的富含伴侣蛋白的肿瘤细胞裂解物（CRCL）是一种有效的疫苗，它包含至少4种高度免疫原性的热休克蛋白（HSP），如HSP70、HSP90、葡萄糖相关蛋白94和钙网蛋白。我们之前已证明，CRCL既提供肿瘤抗原来源，又提供触发树突状细胞（DC）激活的危险信号。用肿瘤来源的CRCL进行免疫可引发肿瘤特异性T细胞反应，从而导致肿瘤消退。在当前研究中，我们进一步剖析了CRCL模拟免疫系统的机制，并证明自然杀伤（NK）细胞是产生有效抗肿瘤作用所必需的。我们的结果表明，CRCL直接刺激NK细胞产生促炎细胞因子和趋化因子，这可能导致肿瘤部位巨噬细胞的激活和募集。因此，本报告进一步深入了解了CRCL作为抗癌免疫刺激剂的功能。
