TY - JOUR
T1 - Systemic and local immunosuppression in patients with high-grade meningiomas
AU - Li, Yuping D.
AU - Veliceasa, Dorina
AU - Lamano, Jason B.
AU - Lamano, Jonathan B.
AU - Kaur, Gurvinder
AU - Biyashev, Dauren
AU - Horbinski, Craig M.
AU - Kruser, Timothy Joseph
AU - Bloch, Orin
N1 - Funding Information:
The authors would like to thank the Nervous System Tumor Bank at Northwestern University, without which the current study would not be possible. Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by National Cancer Institute (NCI) CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center.
Funding Information:
Funding This work was supported by the Howard Hughes Medical Institute Medical Student Research Fellows program (Yuping Li) as well as by the NIH/NCI (National Cancer Institute) R01 (CA164714; Orin Bloch) and NIH/National Institute of Neurological Disorders and Stroke (NINDS) R00 (NS078055; Orin Bloch). The funding was received by National Cancer Institute (CA206413; Jonathan B.
Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
KW - Immune checkpoint inhibition
KW - Immunotherapy
KW - Meningioma
KW - PD-L1
KW - Programmed death-ligand 1
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U2 - 10.1007/s00262-019-02342-8
DO - 10.1007/s00262-019-02342-8
M3 - Article
C2 - 31030234
AN - SCOPUS:85064887145
VL - 68
SP - 999
EP - 1009
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 6
ER -