Authors
Junfei Zhao, Andrew X Chen, Robyn D Gartrell, Andrew M Silverman, Luis Aparicio, Tim Chu, Darius Bordbar, David Shan, Jorge Samanamud, Aayushi Mahajan, Ioan Filip, Rose Orenbuch, Morgan Goetz, Jonathan T Yamaguchi, Michael Cloney, Craig Horbinski, Rimas V Lukas, Jeffrey Raizer, Ali I Rae, Jinzhou Yuan, Peter Canoll, Jeffrey N Bruce, Yvonne M Saenger, Peter Sims, Fabio M Iwamoto, Adam M Sonabend, Raul Rabadan
Publication date
2019/3
Journal
Nature medicine
Volume
25
Issue
3
Pages
462-469
Publisher
Nature Publishing Group US
Description
Immune checkpoint inhibitors have been successful across several tumor types; however, their efficacy has been uncommon and unpredictable in glioblastomas (GBM), where <10% of patients show long-term responses. To understand the molecular determinants of immunotherapeutic response in GBM, we longitudinally profiled 66 patients, including 17 long-term responders, during standard therapy and after treatment with PD-1 inhibitors (nivolumab or pembrolizumab). Genomic and transcriptomic analysis revealed a significant enrichment of PTEN mutations associated with immunosuppressive expression signatures in non-responders, and an enrichment of MAPK pathway alterations (PTPN11, BRAF) in responders. Responsive tumors were also associated with branched patterns of evolution from the elimination of neoepitopes as well as with differences in T cell clonal diversity and tumor microenvironment …
Scholar articles
J Zhao, AX Chen, RD Gartrell, AM Silverman… - Nature medicine, 2019