Inhibiting PP2A Upregulates B7-H3 Expression and Potentially Increases the Sensitivity of Malignant Meningiomas to Immunotherapy by Proteomics.

Abstract

Malignant meningiomas have a high mortality rate and short survival time and currently have no effective treatment. In our study, proteomics analysis was performed to identify highly expressed proteins as therapeutic targets in malignant meningiomas. Cell Counting Kit-8 (CCK-8) assays were performed to verify the effect of LB-100 on the growth of malignant meningiomas. In addition, immunoblotting was used to verify the expression of B7-H3 and phosphorylation of STAT1 (Tyr701) in tissues and cells. Our results show that STAT1 and CD276 (B7-H3) regulated by PP2A were enriched in GO_IMMUNE_EFFECTOR_PROCESS and GO_REGULATION_OF_IMMUNE_SYSTEM_PROCESS. The immunotherapy target protein B7-H3 was confirmed to be upregulated in malignant meningiomas compared with meningothelial (p = 0.0001) and fibroblastic (p = 0.0046) meningiomas. In vitro, the PP2A inhibitor LB-100 suppressed the growth and invasion of malignant meningioma cells. Notably, the PP2A inhibitor LB-100 increased the phosphorylation of STAT1, thereby increasing the expression of the immune checkpoint protein B7-H3 in malignant meningioma cells in vitro. In conclusion, B7-H3 was found to be upregulated in malignant meningiomas. The PP2A inhibitor LB-100 increased the phosphorylation of STAT1 and B7-H3 expression, which could increase the sensitivity of malignant meningiomas to B7-H3 targeted immunotherapy.

• Authors: Boyi Hu, Shuyu Hao, Yazhou Miao, Yuxuan Deng, Jing Wang, Hong Wan, Shaodong Zhang, Nan Ji, Jie Feng
• Journal: Pathology oncology research : POR (Pathol Oncol Res) Vol. 28 Pg. 1610572 ( 2022) ISSN: 1532-2807 [Electronic] Switzerland
• PMID: 36203966 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Hu, Hao, Miao, Deng, Wang, Wan, Zhang, Ji and Feng.

Chemical References

• B7 Antigens
• CD276 protein, human
• Immune Checkpoint Proteins

Topics

• B7 Antigens
• Humans
• Immune Checkpoint Proteins
• Immunotherapy (methods)
• Meningeal Neoplasms (pathology)
• Meningioma (pathology)
• Proteomics