Academy of Mathematics and Systems Science, CAS
Colloquia & Seminars
| | Speaker: | Dr. Junfei Zhao，Aassociate research scientist，Department of Biomedical Informatics at Columbia University.
| | Inviter: | 张世华 研究员 | Title:
| Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma | Time & Venue:
| 2019.09.05 14:00 N219 | 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 longterm 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. | |
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