Maisel Daniela, Birzele Fabian, Voss Edgar, Nopora Adam, Bader Sabine, Friess Thomas, Goller Bernhard, Laifenfeld Daphna, Weigand Stefan, Runza Valeria
Translational Technologies and Bioinformatics, Pharmaceutical Sciences, Roche Innovation Center Munich, Penzberg, Germany.
Discovery Oncology, Roche Innovation Center Munich, Penzberg, Germany.
PLoS One. 2016 Jul 27;11(7):e0159716. doi: 10.1371/journal.pone.0159716. eCollection 2016.
CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system. Using cytokine measurements we further show that this activation involves the secretion of chemo-attractants necessary for the recruitment of immune cells (i.e. macrophages) to the tumor site. We finally provide evidence for antibody-dependent cellular phagocytosis (ADCP) of the malignant cells by macrophages.
CD44是一种据报道参与多种细胞功能的跨膜受体，在多种癌症类型中过度表达，并被认为与这些癌症的发生、发展和预后有关。由于CD44与透明质酸（HA）相互作用受阻后的一系列事件尚未得到详细研究，我们通过RNA测序对异种移植肿瘤进行了分析，以阐明抗CD44抗体RG7356的作用模式。对肿瘤和宿主基因表达谱的分析使我们提出了这样的假设：用RG7356抗体治疗会导致免疫系统激活。通过细胞因子检测，我们进一步表明这种激活涉及分泌趋化因子，这些趋化因子是免疫细胞（即巨噬细胞）募集到肿瘤部位所必需的。我们最终提供了巨噬细胞对恶性细胞进行抗体依赖性细胞吞噬作用（ADCP）的证据。
