Authors
Alejandro Jiménez-Sánchez, 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 Gavarro, 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
Publication date
2020/6
Journal
Nature Genetics
Volume
52
Issue
6
Pages
582-593
Publisher
Nature Publishing Group US
Description
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 …
Scholar articles
A Jiménez-Sánchez, P Cybulska, KLV Mager, S Koplev… - Nature Genetics, 2020