title: Single vs. combination immunotherapeutic strategies for glioma.
abstract: Malignant gliomas are highly invasive tumors, associated with a dismal survival rate despite standard of care, which includes surgical resection, radiotherapy and chemotherapy with temozolomide (TMZ). Precision immunotherapies or combinations of immunotherapies that target unique tumor-specific features may substantially improve upon existing treatments. Areas covered: Clinical trials of single immunotherapies have shown therapeutic potential in high-grade glioma patients, and emerging preclinical studies indicate that combinations of immunotherapies may be more effective than monotherapies. In this review, the authors discuss emerging combinations of immunotherapies and compare efficacy of single vs. combined therapies tested in preclinical brain tumor models. Expert opinion: Malignant gliomas are characterized by a number of factors which may limit the success of single immunotherapies including inter-tumor and intra-tumor heterogeneity, intrinsic resistance to traditional therapies, immunosuppression, and immune selection for tumor cells with low antigenicity. Combination of therapies which target multiple aspects of tumor physiology are likely to be more effective than single therapies. While a limited number of combination immunotherapies are described which are currently being tested in preclinical and clinical studies, the field is expanding at an astounding rate, and endless combinations remain open for exploration.
authors.affiliation: a Department of Neurosurgery , The University of Michigan School of Medicine, MSRB II , Ann Arbor , MI , USA.|b Department of Cell and Developmental Biology , The University of Michigan School of Medicine , Ann Arbor , MI , USA.
authors.forename: Mayuri
authors.initials: M
authors.lastname: Chandran
authors.affiliation: c Instituto de Investigaciones Biomédicas (CONICET-UBA), Facultad de Medicina , Universidad de Buenos Aires , Buenos Aires , Argentina.
authors.forename: Marianela
authors.initials: M
authors.lastname: Candolfi
authors.affiliation: a Department of Neurosurgery , The University of Michigan School of Medicine, MSRB II , Ann Arbor , MI , USA.|b Department of Cell and Developmental Biology , The University of Michigan School of Medicine , Ann Arbor , MI , USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Shah
authors.affiliation: d Department of Neurosurgery , Kyoto University Graduate School of Medicine , Kyoto , Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mineharu
authors.affiliation: a Department of Neurosurgery , The University of Michigan School of Medicine, MSRB II , Ann Arbor , MI , USA.|b Department of Cell and Developmental Biology , The University of Michigan School of Medicine , Ann Arbor , MI , USA.
authors.forename: Viveka Nand
authors.initials: VN
authors.lastname: Yadav
authors.affiliation: a Department of Neurosurgery , The University of Michigan School of Medicine, MSRB II , Ann Arbor , MI , USA.|e Department of Pediatrics, Hematology & Oncology , The University of Michigan School of Medicine , Ann Arbor , MI , USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Koschmann
authors.affiliation: c Instituto de Investigaciones Biomédicas (CONICET-UBA), Facultad de Medicina , Universidad de Buenos Aires , Buenos Aires , Argentina.
authors.forename: Antonela S
authors.initials: AS
authors.lastname: Asad
authors.affiliation: a Department of Neurosurgery , The University of Michigan School of Medicine, MSRB II , Ann Arbor , MI , USA.|b Department of Cell and Developmental Biology , The University of Michigan School of Medicine , Ann Arbor , MI , USA.
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Lowenstein
authors.affiliation: a Department of Neurosurgery , The University of Michigan School of Medicine, MSRB II , Ann Arbor , MI , USA.|b Department of Cell and Developmental Biology , The University of Michigan School of Medicine , Ann Arbor , MI , USA.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Castro
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003131:Combined Modality Therapy / Q000379:methods; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D000077204:Temozolomide
chemical_list: D019496:Cancer Vaccines; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Glioma; cancer vaccines; gene therapy; immune checkpoint blockade; immunotherapy