Cancer immunology of brain tumors

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Although understanding of brain cancer advanced significantly and diagnosis by IDH1 R132H IHC assessment improved dramatically, the mortality rate for brain cancer has still remained consistent for many decades. Now brain cancer is one of the main cancer types for which new immunotherapy treatment options are being developed. Thereby brain cancer has remained a significant challenge due to the blood-brain barrier exclusion of many immune cells from the central nervous system and the profoundly immunosuppressive brain tumor microenvironment. So far cancer immunotherapy has emerged as a highly effective approach for the treatment of several types of other advanced cancers, including lung cancer, melanoma and lymphoma. Two immunotherapies for brain and nervous system cancers have been approved: Bevacizumab for adults, and dinutuximab for children. Different brain cancer immunotherapies which are being tested in clinical trials focus on checkpoint inhibitors, besides other e.g. cancer vaccines, oncolytic viruses and monoclonal antibodies.

Glioblastoma and other brain tumors generate a varied immune response and investigation of the immune microenvironment may lead to novel immunotherapy treatments modalities. We believe that the complex evaluation of immunologic marker profiles (e.g. CD3, CD8, Fox-3) integrating immune checkpoint proteins (e.g. PD1, PDL1, CTLA4, TIGIT) accompanied by an assessment of their relationship to molecular characteristics of glioma (MGMT promoter methylation status and ATRX, p53, and IDH1 mutation status) will be crucial for the evaluation of interrelations with potential clinical significance. An understanding of the association of cancer immunology markers with the molecular character of brain tumor tissue specimen may help to identify promising targets for immunotherapy options in brain cancer.

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