title: Microenvironmental clues for glioma immunotherapy.
abstract: Gliomas have been viewed for decades as inaccessible for a meaningful antitumor immune response as they grow in a sanctuary site protected from infiltrating immune cells. Moreover, the glioma microenvironment constitutes a hostile environment for an efficient antitumor immune response as glioma-derived factors such as transforming growth factor β and catabolites of the essential amino acid tryptophan paralyze T-cell function. There is growing evidence from preclinical and clinical studies that a meaningful antitumor immunity exists in glioma patients and that it can be activated by vaccination strategies. As a consequence, the concept of glioma immunotherapy appears to be experiencing a renaissance with the first phase 3 randomized immunotherapy trials entering the clinical arena. On the basis of encouraging results from other tumor entities using immunostimulatory approaches by blocking endogenous T-cell suppressive pathways mediated by cytotoxic T-lymphocyte antigen 4 or programmed cell death protein 1/programmed cell death protein 1 ligand 1 with humanized antibodies, there is now a realistic and promising option to combine active immunotherapy with agents blocking the immunosuppressive microenvironment in patients with gliomas to allow a peripheral antitumor immune response induced by vaccination to become effective. Here we review the current clinical and preclinical evidence of antimicroenvironment immunotherapeutic strategies in gliomas.
authors.affiliation: Department of Neurooncology, University Hospital Heidelberg and National Center for Tumor Diseases, German Cancer Consortium (DKTK) Clinical Cooperation Units, Im Neuenheimer Feld, Heidelberg, Germany, michael.platten@med.uni-heidelberg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Platten
authors.forename: Katharina
authors.initials: K
authors.lastname: Ochs
authors.forename: Dieter
authors.initials: D
authors.lastname: Lemke
authors.forename: Christiane
authors.initials: C
authors.lastname: Opitz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D005910:Glioma / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D059016:Tumor Microenvironment / Q000502:physiology*