Systemic and local immunosuppression in patients with high-grade meningiomas

Yuping D. Li, Dorina Veliceasa, Jason B. Lamano, Jonathan B. Lamano, Gurvinder Kaur, Dauren Biyashev, Craig M. Horbinski, Tim J. Kruser, Orin Bloch

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Aim: Despite current treatments, high-grade meningiomas continue to have a poor prognosis. Immunotherapy targeting immune checkpoints, such as PD-L1, has demonstrated significant success in controlling numerous malignancies. In this study, we investigate the extent of systemic and local immunosuppression in meningiomas to assess the potential benefit of immune checkpoint inhibitors for the treatment of high-grade meningiomas. Methods: Peripheral blood was collected from patients undergoing resection of meningiomas (WHO grade I, n = 18; grade II, n = 25; grade III, n = 10). Immunosuppressive myeloid cells (CD45+CD11b+PD-L1+), myeloid-derived suppressor cells (MDSCs) (CD11b+CD33+HLA-DRlow), and regulatory T cells (Tregs) (CD3+CD4+CD25+FoxP3+) were quantified through flow cytometry. Tissue sections from the same patients were assessed for PD-L1 expression and T cell infiltration via immunohistochemistry. Results: Patients with grade III meningiomas demonstrated increased peripheral monocyte PD-L1 compared to patients with grade I/II meningiomas and healthy controls. Peripheral MDSC abundance was increased in grades II and III meningioma patients. PD-L1 staining of meningioma tissue demonstrated increased positivity in grade III meningiomas. Intratumoral PD-L1 was not associated with progression-free survival. High-grade meningiomas had increased T-cell infiltration. However, a significant proportion of these T cells were exhausted PD1+ T cells and immunosuppressive Tregs. Conclusions: Patients with meningiomas exhibit signs of peripheral immunosuppression, including increased PD-L1 on myeloid cells and elevated MDSC abundance proportional to tumor grade. Additionally, the tumors express substantial PD-L1 proportional to tumor grade. These results suggest a role for immune checkpoint inhibitors targeting the PD-L1/PD-1 pathway in combination with standard therapies for the treatment of high-grade meningiomas.

Original languageEnglish (US)
Pages (from-to)999-1009
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume68
Issue number6
DOIs
StatePublished - Jun 1 2019

    Fingerprint

Keywords

  • Immune checkpoint inhibition
  • Immunotherapy
  • Meningioma
  • PD-L1
  • Programmed death-ligand 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Li, Y. D., Veliceasa, D., Lamano, J. B., Lamano, J. B., Kaur, G., Biyashev, D., Horbinski, C. M., Kruser, T. J., & Bloch, O. (2019). Systemic and local immunosuppression in patients with high-grade meningiomas. Cancer Immunology, Immunotherapy, 68(6), 999-1009. https://doi.org/10.1007/s00262-019-02342-8