Journal
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
Volume 14, Issue 4, Pages -Publisher
SPRINGER
DOI: 10.1007/s11910-014-0440-1
Keywords
Tryptophan; Kynurenine; Tryptophan 2,3-dioxygenase; Indoleamine 2,3-dioxygenase; Aryl hydrocarbon receptor; Cytotoxic T-lymphocyte antigen 4; Programmed cell death protein 1
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Funding
- German Cancer Aid [110392]
- German Research Foundation [SFB938 TP K]
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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 beta 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.
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