PRJNA566392
Tumoral and immune heterogeneity in PD-1 responsive glioblastoma: a case study
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 benefited from checkpoint blockade with an unusually long 25-month 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, and a uniform loss of focal amplifications in EGFR. Comparisons with recently reported correlates of checkpoint blockade in glioblastoma and with TCGA-GBM revealed appreciable intra-tumoral heterogeneity that may contribute to a differential PD-1 blockade response.