title: Immunotherapy advances for glioblastoma.
abstract: Survival for patients with glioblastoma, the most common high-grade primary CNS tumor, remains poor despite multiple therapeutic interventions including intensifying cytotoxic therapy, targeting dysregulated cell signaling pathways, and blocking angiogenesis. Exciting, durable clinical benefits have recently been demonstrated for a number of other challenging cancers using a variety of immunotherapeutic approaches. Much modern research confirms that the CNS is immunoactive rather than immunoprivileged. Preliminary results of clinical studies demonstrate that varied vaccine strategies have achieved encouraging evidence of clinical benefit for glioblastoma patients, although multiple variables will likely require systematic investigation before optimal outcomes are realized. Initial preclinical studies have also revealed promising results with other immunotherapies including cell-based approaches and immune checkpoint blockade. Clinical studies to evaluate a wide array of immune therapies for malignant glioma patients are being rapidly developed. Important considerations going forward include optimizing response assessment and identifiying correlative biomarkers for predict therapeutic benefit. Finally, the potential of complementary combinatorial immunotherapeutic regimens is highly exciting and warrants expedited investigation.
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts (G.F., C.W., K.W.W.); Department of Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., C.W.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (E.A.C.); Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (P.Y.W.); Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina (J.H.S.); Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (W.T.C.); Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (C.W., E.F.F., G.D.); Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (G.D.).
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts (G.F., C.W., K.W.W.); Department of Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., C.W.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (E.A.C.); Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (P.Y.W.); Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina (J.H.S.); Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (W.T.C.); Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (C.W., E.F.F., G.D.); Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (G.D.).
authors.forename: Gordon
authors.initials: G
authors.lastname: Freeman
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts (G.F., C.W., K.W.W.); Department of Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., C.W.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (E.A.C.); Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (P.Y.W.); Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina (J.H.S.); Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (W.T.C.); Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (C.W., E.F.F., G.D.); Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (G.D.).
authors.forename: Catherine
authors.initials: C
authors.lastname: Wu
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts (G.F., C.W., K.W.W.); Department of Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., C.W.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (E.A.C.); Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (P.Y.W.); Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina (J.H.S.); Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (W.T.C.); Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (C.W., E.F.F., G.D.); Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (G.D.).
authors.forename: E Antonio
authors.initials: EA
authors.lastname: Chiocca
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts (G.F., C.W., K.W.W.); Department of Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., C.W.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (E.A.C.); Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (P.Y.W.); Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina (J.H.S.); Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (W.T.C.); Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (C.W., E.F.F., G.D.); Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (G.D.).
authors.forename: Kai W
authors.initials: KW
authors.lastname: Wucherpfennig
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts (G.F., C.W., K.W.W.); Department of Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., C.W.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (E.A.C.); Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (P.Y.W.); Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina (J.H.S.); Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (W.T.C.); Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (C.W., E.F.F., G.D.); Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (G.D.).
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts (G.F., C.W., K.W.W.); Department of Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., C.W.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (E.A.C.); Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (P.Y.W.); Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina (J.H.S.); Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (W.T.C.); Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (C.W., E.F.F., G.D.); Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (G.D.).
authors.forename: Edward F
authors.initials: EF
authors.lastname: Fritsch
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts (G.F., C.W., K.W.W.); Department of Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., C.W.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (E.A.C.); Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (P.Y.W.); Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina (J.H.S.); Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (W.T.C.); Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (C.W., E.F.F., G.D.); Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (G.D.).
authors.forename: William T
authors.initials: WT
authors.lastname: Curry
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts (G.F., C.W., K.W.W.); Department of Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., C.W.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (E.A.C.); Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (P.Y.W.); Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina (J.H.S.); Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (W.T.C.); Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (C.W., E.F.F., G.D.); Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (G.D.).
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.affiliation: Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., P.Y.W.); Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts (G.F., C.W., K.W.W.); Department of Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (D.A.R., C.W.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (E.A.C.); Division of Neuro-Oncology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (P.Y.W.); Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina (J.H.S.); Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (W.T.C.); Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (C.W., E.F.F., G.D.); Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (G.D.).
authors.forename: Glenn
authors.initials: G
authors.lastname: Dranoff
mesh_terms: D000818:Animals; D005909:Glioblastoma / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy
keywords: glioblastoma; immune checkpoint; immunosuppression; immunotherapy; vaccine