Table 3.

High priority questions for increasing immunotherapeutic efficacy against tumors in the CNS.

Preclinical
• Do inhibitors that co-target IDO1 and IDO2 provide superior efficacy when compared to monotherapy? • Will inhibitors of tryptophan catabolism complement other immunotherapies? • Which capacity of IDO1 is more important for immunotherapeutic efficacy: signal transduction modifier vs. tryptophan catabolism? • What is the best approach for further identification of ubiquitous GBM-specific neoantigens for translation into vaccine and/or adoptive T cell therapeutic approaches? • Is there an optimal vaccination approach to generate functional T cell responses and is this GBM subtype-specific (i.e. responsiveness in classical vs. mesenchymal, newly diagnosed vs. recurrent)? • Do different GBM subtypes possess correlative mutational frequencies that associate with responsiveness to immunotherapy? • Will survival outcomes be enhanced with combinatorial approaches (vaccine ± RT ± checkpoint blockade ± STING activation)?
Clinical
• Will GBM respond to immune checkpoint blockade? • What is the best approach for identifying patient cohorts that will benefit from immunotherapy? • What is the best approach for monitoring treatment effectiveness in GBM patients to immunotherapy (i.e. peripheral blood markers, tryptophan metabolic profiling or IHC markers in the tumor)? • What is the best approach to limit brain swelling following immunotherapy? Is bevacizumab an alternative to decadron that can be easily added without defusing effectiveness?