Immunological challenges for peptide-based immunotherapy in glioblastoma.
Glioblastoma is the most aggressive primary tumor of the central nervous system with a medium overall survival of 7-15 months after diagnosis. Since tumor cells penetrate the surrounding brain tissue, complete surgical resection is impossible and tumor recurrence is almost a certainty. New treatment modalities are therefore needed, and these should be able to trace, identify, and kill dispersed tumor cells with great accuracy. Immunological approaches in principle meet these needs. Unfortunately, due to profound tumor-associated mechanisms of immunosuppression and -evasion, immunotherapeutic strategies like peptide vaccination have so far not been translated into clinical success. If future, peptide-based vaccination approaches shall be successful in glioblastoma therapy, multiple questions need to be solved including identification of suitable antigens, route and mode of vaccination, preparation of the tumor-bearing "host" and antagonizing, as much as this is possible, glioblastoma-associated mechanisms of immune evasion and poor vaccination response. In this review we will address the immunological challenges of glioblastoma and discuss key aspects that have rendered successful immunotherapy difficult in the past.
Department of Neurosurgery, University Hospital Zurich, 8091 Zurich, Switzerland; Center for Molecular Neurobiology Hamburg, University Medical Center Eppendorf, 20251 Hamburg, Germany. Electronic address: malte.mohme@zmnh.uni-hamburg.de.
Malte
M
Mohme
Marian C
MC
Neidert
Luca
L
Regli
Michael
M
Weller
Roland
R
Martin
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D002986:Clinical Trials as Topic; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D010455:Peptides / Q000276:immunology / Q000627:therapeutic use*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D010455:Peptides
Anti-tumor response; Glioblastoma; Glioma; Immunotherapy; Peptide-vaccination; Tumor immunology