Intratumoral B cell and interferon signatures in newly diagnosed glioblastoma are associated with longer survival in patients treated with SurVaxM.

Abstract

Glioblastoma (GBM) has proved difficult to treat, and there is dire need for more effective therapies. In a single arm phase IIa trial (NCT02455557), treatment of newly diagnosed GBM patients with the peptide vaccine SurVaxM resulted in promising median progression-free and overall survival. To investigate molecular features that associate with GBM responsiveness to SurVaxM, retrospective whole exome and RNA sequencing was performed on patient tumors (n&#x2009;=&#x2009;34) collected prior to standard of care treatment plus SurVaxM. Differential gene expression and mutational profiles were characterized between patients with short-term (OS&#x2009;<&#x2009;18&#xa0;months) or long-term (OS&#x2009;&#x2265;&#x2009;18&#xa0;months) overall survival. Greater expression of interferon, complement, and humoral immunity signatures were associated with long-term survival. Deconvolution of transcriptomes identified enrichment of intratumoral memory B cell populations in long-term survivors that were validated by CD20 staining in matched samples. A five-gene expression signature and a B cell specific signature predicted survival within the SurVaxM-treated cohort, however, these signatures were not associated with improved outcomes in a similarly treated population obtained from The Cancer Genome Atlas (TCGA) that did not receive immunotherapeutic intervention. Although prospective validation is ongoing, the findings in this discovery cohort specify molecular features of GBM associated with better overall survival and potential responsiveness to immunotherapy with SurVaxM.