Very Low Tumor Mutation Burden Identifies Inflamed Recurrent Glioblastomas Responsive to Cancer Immunotherapy

A subset of available tumors (with matched blood) from patients enrolled in a phase I clinical trial testing a recombinant poliovirus, published by Desjardins et al. NEJM 2018 (PMID:29943666), were analyzed by whole exome sequencing and RNA-seq. It was discovered that low tumor mutation burden correlated with survival outcome, and also discovered that low tumor mutation burden correlated with higher inflammatory gene signatures by RNA-seq.

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All patients enrolled in the phase I PVSRIPO clinical trial (NCT01491893) with available tumor specimens were included in this study. For the purpose of survival comparisons to low tumor mutation burden and inflammatory gene signatures, only specimens procured at the time of PVSIRPO administration were analyzed. For comparison of TP53 mutation status and survival, all available specimens at any time point were used to define TP53 mutation status.

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Phase I clinical trial specimens were procured at Duke University from 2012-2018, Nucleic acids were isolated at Duke University or Tempus Labs. Samples were sequenced on an llumina Hi-seq 4000 system using patterned flow cell technology at Tempus, Inc. ]]>