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Expression and prognostic impact of immune modulatory molecule PD-L1 in meningioma

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Abstract

While immunotherapy may offer promising new approaches for high grade meningiomas, little is currently known of the immune landscape in meningiomas. We sought to characterize the immune microenvironment and a potentially targetable antigen mesothelin across WHO grade I-III cases of meningiomas, and how infiltrating immune populations relate to patient outcomes. Immunohistochemistry was performed on tissue microarrays constructed from 96 meningioma cases. The cohort included 16 WHO grade I, 62 WHO grade II, and 18 WHO grade III tumors. Immunohistochemistry was performed using antibodies against CD3, CD8, CD20, CD68, PD-L1, and mesothelin. Dual staining using anti-PD-L1 and anti-CD68 antibodies was performed, and automated cell detection and positive staining detection algorithms were utilized. Greater degree of PD-L1 expression was found in higher grade tumors. More specifically, higher grade tumors contained increased numbers of intratumoral CD68−, PD-L1+ cells (p = 0.022), but did not contain higher numbers of infiltrating CD68+, PD-L1+ cells (p = 0.30). Higher PD-L1+/CD68− expression was independently predictive of worse overall survival in our cohort when accounting for grade, performance status, extent of resection, and recurrence history (p = 0.014). Higher expression of PD-L1+/CD68− was also present in tumors that had undergone prior radiotherapy (p = 0.024). Approximately quarter of meningiomas overexpressed mesothelin to levels equivalent to those found in pancreatic carcinomas and malignant mesotheliomas. The association with poor survival outcomes in our study suggests that PD-L1 may play a significant biologic role in the aggressive phenotype of higher grade meningiomas. Thus, immunotherapeutic strategies such as checkpoint inhibition may have clinical utility in PD-L1 overexpressing meningiomas.

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Funding

Dr. Han is supported by the Neurosurgery Research and Education Foundation Research Fellowship and the Hanson Foundation for Meningioma Research.

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Authors and Affiliations

  1. Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Ave, M-779, San Francisco, CA, 94143, USA

    Seunggu J. Han, Gary Kohanbash, Shruti Shrivastav, Stephen T. Magill, Annette M. Molinaro, Michael W. McDermott, Philip V. Theodosopoulos, Manish K. Aghi, Mitchel S. Berger, Nicholas A. Butowski, Joanna J. Phillips, Arie Perry & Hideho Okada

  2. Department of Pathology, Division of Neuropathology, University of California, San Francisco, San Francisco, CA, USA

    Gerald Reis, Joanna J. Phillips & Arie Perry

  3. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA

    Annette M. Molinaro

  4. Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA

    Igor Barani

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  1. Seunggu J. Han
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Correspondence to Seunggu J. Han.

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Han, S.J., Reis, G., Kohanbash, G. et al. Expression and prognostic impact of immune modulatory molecule PD-L1 in meningioma. J Neurooncol 130, 543–552 (2016). https://doi.org/10.1007/s11060-016-2256-0

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