Identification of PD-L2, B7-H3 and CTLA-4 immune checkpoint proteins in genetic subtypes of meningioma

• Main Authors: Dustin T Proctor, Zeel Patel, Sanju Lama, Lothar Resch, Guido van Marle, Garnette R Sutherland
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2019-01-01
• Series: OncoImmunology
• Subjects: meningioma; immune checkpoint protein; pd-l1; pd-l2; b7-h3; ctla-4; pi3k/akt/mtor; immunotherapy; brain tumor
• Online Access: http://dx.doi.org/10.1080/2162402X.2018.1512943

Meningioma is the most common brain tumor in adults. Surgical resection remains the primary treatment. No chemotherapy exists. However, gene mutations now could explain ~ 80% of meningioma and targeted therapies based on these are being investigated. Furthermore, with the recent discovery of PD-L1 in malignant meningioma, clinical trials using immunotherapy have commenced. Here, we report for the first time the expression profiles of immune checkpoint proteins PD-L2, B7-H3 and CTLA-4 in meningioma and their association to common gene mutations. PD-L2 and B7-H3 expression was significantly greater than all immune checkpoint proteins studied, and particularly elevated in patients with gene mutations affecting the PI3K/AKT/mTOR pathway. CTLA-4 expressing CD3+ lymphocytes were observed in atypical and malignant meningioma and tumors harboring a PIK3CA or SMO mutation. These results identify novel targets for immunotherapy irrespective of grade and distinguish potential patient populations based on genetic classification for stratification into checkpoint inhibitor clinical trials.