Abstract
Clinical benefit of immune checkpoint blockade in glioblastoma (GBM) is rare, and we hypothesize that tumor clonal evolution and the immune microenvironment are key determinants of response. Here, we present a detailed molecular characterization of the intratumoral and immune heterogeneity in an IDH wild-type, MGMT-negative GBM patient who plausibly benefited from anti-PD-1 therapy with an unusually long 25-mo overall survival time. We leveraged multiplex immunohistochemistry, RNA-seq, and whole-exome data from the primary tumor and three resected regions of recurrent disease to survey regional tumor-immune interactions, genomic instability, mutation burden, and expression profiles. We found significant regional heterogeneity in the neoantigenic and immune landscape, with a differential T-cell signature among recurrent sectors, a uniform loss of focal amplifications in EGFR, and a novel subclonal EGFR mutation. Comparisons with recently reported correlates of checkpoint blockade in GBM and with TCGA-GBM revealed appreciable intratumoral heterogeneity that may have contributed to a differential PD-1 blockade response.
Original language | English (US) |
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Article number | a004762 |
Journal | Cold Spring Harbor Molecular Case Studies |
Volume | 6 |
Issue number | 2 |
DOIs | |
State | Published - Apr 1 2020 |
Externally published | Yes |
Keywords
- Glioblastoma
- Glioblastoma multiforme
ASJC Scopus subject areas
- General Medicine