Turrini Eleonora, Catanzaro Elena, Muraro Manuele G, Governa Valeria, Trella Emanuele, Mele Valentina, Calcabrini Cinzia, Morroni Fabiana, Sita Giulia, Hrelia Patrizia, Tacchini Massimo, Fimognari Carmela
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Rimini, Italy.
Oncology Surgery, Department of Biomedicine, University Hospital of Basel and University of Basel, ZLF, Basel-Switzerland.
Oncotarget. 2018 May 11;9(36):24443-24456. doi: 10.18632/oncotarget.25325.
The ability of anticancer treatments to promote the activation of tumor-reactive adaptive immune responses is emerging as a critical requirement underlying their clinical effectiveness. We investigated the ability of , a promising anticancer botanical drug, to stimulate immunogenic cell death in a human colorectal cancer cell line (DLD1). Here we show that treatment induces tumor cell cytotoxicity characterized by surface expression of calreticulin, increased HSP70 expression and release of ATP and HMGB1. Remarkably, the exposure to released ICD-inducer factors from -treated DLD1 cells caused a modest induction of CD14-derived dendritic cells maturation, as demonstrated by the increased expression of CD83. Moreover, at sub-toxic concentrations, H.i. treatment of monocytes and dendritic cells induced their mild activation, suggesting its additional direct immunostimulatory activity. These data indicate that induces immunogenic cell death in human tumor cells and suggest its potential relevance in innovative cancer immunotherapy protocols.
抗癌治疗促进肿瘤反应性适应性免疫反应激活的能力正成为其临床有效性的关键要求。我们研究了一种有前景的抗癌植物药刺激人结肠癌细胞系(DLD1)发生免疫原性细胞死亡的能力。在此我们表明,该药物治疗诱导肿瘤细胞毒性,其特征为钙网蛋白的表面表达、HSP70表达增加以及ATP和HMGB1的释放。值得注意的是,暴露于经该药物处理的DLD1细胞释放的诱导免疫原性细胞死亡的因子会导致CD14来源的树突状细胞适度成熟,这通过CD83表达增加得以证明。此外,在亚毒性浓度下,该药物对单核细胞和树突状细胞的处理诱导了它们的轻度激活,表明其具有额外的直接免疫刺激活性。这些数据表明该药物在人肿瘤细胞中诱导免疫原性细胞死亡,并表明其在创新癌症免疫治疗方案中的潜在相关性。