Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma.

Resource Type: 
Publication
Publication Type: 
Journal Article
Title: 
Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma.
Authors: 
Zhao J, Chen AX, Gartrell RD, Silverman AM, Aparicio L, Chu T, Bordbar D, Shan D, Samanamud J, Mahajan A, Filip I, Orenbuch R, Goetz M, Yamaguchi JT, Cloney M, Horbinski C, Lukas RV, Raizer J, Rae AI, Yuan J, Canoll P, Bruce JN, Saenger YM, Sims P, Iwamoto FM, Sonabend AM, Rabadan R
Series Name: 
Nature medicine
Journal Abbreviation: 
Nat Med
Volume: 
25
Issue: 
3
Page Numbers: 
462-469
Publication Year: 
2019
Publication Date: 
2019 03
DOI: 
10.1038/s41591-019-0349-y
ISSN: 
1546-170X
EISSN: 
1546-170X
Cross Reference: 
PMIDLoading content
Citation: 
Zhao J, Chen AX, Gartrell RD, Silverman AM, Aparicio L, Chu T, Bordbar D, Shan D, Samanamud J, Mahajan A, Filip I, Orenbuch R, Goetz M, Yamaguchi JT, Cloney M, Horbinski C, Lukas RV, Raizer J, Rae AI, Yuan J, Canoll P, Bruce JN, Saenger YM, Sims P, Iwamoto FM, Sonabend AM, Rabadan R. Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma.. Nature medicine. 2019 03; 25(3):462-469.
Abstract: 

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 profiles. Our study shows that clinical response to anti-PD-1 immunotherapy in GBM is associated with specific molecular alterations, immune expression signatures, and immune infiltration that reflect the tumor's clonal evolution during treatment.

Publication Model: 
Print-Electronic
Language: 
English
Language Abbr: 
eng
Journal Country: 
United States