小柯机器人

美国德克萨斯大学西南医学中心傅阳心、乔健等研究人员合作取得新进展。他们的最新工作表明，肿瘤细胞通过劫持caspase 9信号来抑制辐射诱导的免疫反应。这一研究成果于2020年3月30日在线发表在国际学术期刊《自然—免疫学》上。

Title: Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling

Author: Chuanhui Han, Zhida Liu, Yunjia Zhang, Aijun Shen, Chunbo Dong, Anli Zhang, Casey Moore, Zhenhua Ren, Changzheng Lu, Xuezhi Cao, Chun-Li Zhang, Jian Qiao, Yang-Xin Fu

Issue&Volume: 2020-03-30

Abstract: High-dose radiation activates caspases in tumor cells to produce abundant DNA fragments for DNA sensing in antigen-presenting cells, but the intrinsic DNA sensing in tumor cells after radiation is rather limited. Here we demonstrate that irradiated tumor cells hijack caspase 9 signaling to suppress intrinsic DNA sensing. Instead of apoptotic genomic DNA, tumor-derived mitochondrial DNA triggers intrinsic DNA sensing. Specifically, loss of mitochondrial DNA sensing in Casp9/ tumors abolishes the enhanced therapeutic effect of radiation. We demonstrated that combining emricasan, a pan-caspase inhibitor, with radiation generates synergistic therapeutic effects. Moreover, loss of CASP9 signaling in tumor cells led to adaptive resistance by upregulating programmed death-ligand 1 (PD-L1) and resulted in tumor relapse. Additional anti-PD-L1 blockade can further overcome this acquired immune resistance. Therefore, combining radiation with a caspase inhibitor and anti-PD-L1 can effectively control tumors by sequentially blocking both intrinsic and extrinsic inhibitory signaling.

DOI: 10.1038/s41590-020-0641-5

Source: https://www.nature.com/articles/s41590-020-0641-5

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex