期刊
ONCOTARGET
卷 6, 期 7, 页码 4704-4716出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3082
关键词
meningioma; PD-L1; RNAscope; immunotherapy
资金
- National Institutes of Health [RO1 GM089652]
- Center for Immune Oncology at the Dana Farber Cancer Institute
- Brain Science Foundation
- Jared Branfman Sunflowers for Life Fund for Pediatric Brain and Spinal Cancer Research
- V Foundation
- King Abdulaziz City for Science and Technology (KACST), Saudi Arabia
There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing significant and durable clinical responses in patients with treatment refractory high-grade tumors. We examined the immune infiltrate of 291 meningiomas including WHO grade I-III meningiomas using immunohistochemistry and we examined the expression of PD-L1 mRNA by RNAscope in situ hybridization and PD-L1 protein by immunohistochemistry. In meningioma, the tumor infiltrating lymphocytes are predominantly T cells. In anaplastic meningioma, there is a sharp decrease in the number of T cells, including the numbers of CD4+ and CD8+ T cells and cells expressing PD-1 and there is also an increase in the number of FOXP3 expressing immunoregulatory (Treg) cells. PD-L1 expression is increased in anaplastic meningioma - both mRNA and protein. Using patient derived meningioma cell, we confirm that PD-L1 is expressed in meningioma cells themselves, and not solely in infiltrating immune cells. This work indicates that high-grade meningioma harbor an immunosuppressive tumor microenviroment and that increased Treg cells and elevated PD-L1 may contribute to the aggressive phenotype of these tumors.
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