Department of Infection, Division of Infection & Immunity, University College London (UCL), Cruciform Building, 90 Gower Street, London WC1E 6BT, UK.
Department of Veterinary Sciences, Polo Universitario dell'Annunziata, University of Messina, Messina 98168, Italy.
Cancer Cell. 2018 Apr 9;33(4):620-633.e6. doi: 10.1016/j.ccell.2018.03.003.
The canine transmissible venereal tumor (CTVT) is a clonally transmissible cancer that regresses spontaneously or after treatment with vincristine, but we know little about the regression mechanisms. We performed global transcriptional, methylation, and functional pathway analyses on serial biopsies of vincristine-treated CTVTs and found that regression occurs in sequential steps; activation of the innate immune system and host epithelial tissue remodeling followed by immune infiltration of the tumor, arrest in the cell cycle, and repair of tissue damage. We identified CCL5 as a possible driver of CTVT regression. Changes in gene expression are associated with methylation changes at specific intragenic sites. Our results underscore the critical role of host innate immunity in triggering cancer regression.
犬传染性性病肿瘤（CTVT）是一种克隆性传播的癌症，可自发消退或经长春新碱治疗后消退，但我们对消退机制知之甚少。我们对长春新碱治疗的 CTVT 的连续活检进行了全局转录组、甲基化和功能途径分析，发现消退是分阶段发生的；先天免疫系统和宿主上皮组织重塑的激活，随后是肿瘤的免疫浸润、细胞周期停滞和组织损伤修复。我们鉴定出 CCL5 可能是 CTVT 消退的驱动因素之一。基因表达的变化与特定内含子位点的甲基化变化相关。我们的研究结果强调了宿主先天免疫在触发癌症消退方面的关键作用。
