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晚期卵巢癌的肿瘤免疫异质性揭示出化疗的免疫原性作用
作者:小柯机器人 发布时间:2020/6/2 20:42:40

英国剑桥大学Martin L. Miller研究组的最近工作表明,晚期卵巢癌的肿瘤免疫异质性揭示出化疗的免疫原性作用。相关论文于2020年6月1日在线发表于《自然—遗传学》。

为了表征高级别浆液性卵巢癌(HGSOC)在新辅助化疗(NACT)前后的肿瘤-免疫界面,研究人员对化疗前后的未经治疗和配对样品进行了免疫基因组分析。在未进行过治疗的HGSOC中,研究人员发现免疫细胞排斥和炎性微环境共存于同一个体和同一肿瘤部位内,表明免疫细胞浸润无处不在。

肿瘤微环境细胞组成、DNA拷贝数、突变和基因表达的分析表明,免疫细胞排斥与未治疗HGSOC中Myc靶基因的扩增和经典Wnt信号表达的增加有关。NACT之后,自然杀伤细胞浸润的增加以及T细胞的寡克隆扩增被检测到。

研究人员证明,晚期HGSOC的肿瘤免疫微环境在本质上是异质的,化学疗法可诱导局部免疫激活,这表明化学疗法可以增强免疫排斥型HGSOC肿瘤的免疫原性。

据了解,在转移性癌症中,肿瘤微环境及其分子基础的异质性程度仍未得到充分研究。

附:英文原文

Title: Unraveling tumor–immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy

Author: Alejandro Jimnez-Snchez, Paulina Cybulska, Katherine LaVigne Mager, Simon Koplev, Oliver Cast, Dominique-Laurent Couturier, Danish Memon, Pier Selenica, Ines Nikolovski, Yousef Mazaheri, Yonina Bykov, Felipe C. Geyer, Geoff Macintyre, Lena Morrill Gavarr, Ruben M. Drews, Michael B. Gill, Anastasios D. Papanastasiou, Ramon E. Sosa, Robert A. Soslow, Tyler Walther, Ronglai Shen, Dennis S. Chi, Kay J. Park, Travis Hollmann, Jorge S. Reis-Filho, Florian Markowetz, Pedro Beltrao, Hebert Alberto Vargas, Dmitriy Zamarin, James D. Brenton, Alexandra Snyder, Britta Weigelt, Evis Sala, Martin L. Miller

Issue&Volume: 2020-06-01

Abstract: In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor–immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory microenvironments coexist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of TME cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following NACT, increased natural killer (NK) cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor–immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors.

DOI: 10.1038/s41588-020-0630-5

Source: https://www.nature.com/articles/s41588-020-0630-5

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex