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

Dustin T Proctor; Zeel Patel; Sanju Lama; Lothar Resch; Guido van Marle; Garnette R Sutherland

doi:10.1080/2162402X.2018.1512943

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

Oncoimmunology. 2018 Sep 5;8(1):e1512943. doi: 10.1080/2162402X.2018.1512943. eCollection 2019.

Authors

Dustin T Proctor^{1

2

3}, Zeel Patel^{1

2

3}, Sanju Lama^{1

2

3}, Lothar Resch⁴, Guido van Marle⁵, Garnette R Sutherland^{1

2

3}

Affiliations

¹ Project neuroArm, Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
² Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
³ Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.
⁴ Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
⁵ Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Abstract

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.

Keywords: B7-H3; CTLA-4; Meningioma; PD-L1; PD-L2; PI3K/AKT/mTOR; brain tumor; immune checkpoint protein; immunotherapy.

Publication types

Research Support, Non-U.S. Gov't

Grants and funding

This study was funded in part from Advancing iMRI, Western Economic Diversification and Calgary Health Trust.