title: PI3K pathway inhibitors: potential prospects as adjuncts to vaccine immunotherapy for glioblastoma.
abstract: Constitutive activation of the PI3K pathway has been implicated in glioblastoma (GBM) pathogenesis. Pharmacologic inhibition can both inhibit tumor survival and downregulate expression of programmed death ligand-1, a protein highly expressed on glioma cells that strongly contributes to cancer immunosuppression. In that manner, PI3K pathway inhibitors can help optimize GBM vaccine immunotherapy. In this review, we describe and assess the potential integration of various classes of PI3K pathway inhibitors into GBM immunotherapy. While early-generation inhibitors have a wide range of immunosuppressive effects that could negate their antitumor potency, further work should better characterize how contemporary inhibitors affect the immune response. This will help determine if these inhibitors are truly a therapeutic avenue with a strong future in GBM immunotherapy.
authors.affiliation: Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Feinberg School of Medicine, 676 N St Clair Street, Suite 2210, Chicago, IL 60611-2911, USA.
authors.forename: Taemin
authors.initials: T
authors.lastname: Oh
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ivan
authors.forename: Matthew Z
authors.initials: MZ
authors.lastname: Sun
authors.forename: Michael
authors.initials: M
authors.lastname: Safaee
authors.forename: Shayan
authors.initials: S
authors.lastname: Fakurnejad
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Clark
authors.forename: Eli T
authors.initials: ET
authors.lastname: Sayegh
authors.forename: Orin
authors.initials: O
authors.lastname: Bloch
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Parsa
mesh_terms: D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology* / Q000628:therapy; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000276:immunology / Q000627:therapeutic use; D005909:Glioblastoma / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007167:Immunotherapy; D018448:Models, Immunological; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; D019496:Cancer Vaccines; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C423236:CD274 protein, human
keywords: PI3K pathway inhibitor; cancer; glioblastoma; immunotherapy; treatment; vaccine