Anaplastic meningioma is classified as a World Health Organization (WHO) grade III tumor and shows a strong tendency to recur. Although the incidence of anaplastic meningioma is low, the high rate of recurrence and death still makes treatment a challenge. A proteomics analysis was performed to investigate the differentially expressed proteins between anaplastic meningiomas and fibrous meningiomas by micro-LC-MS/MS. The key metabolic enzyme nicotinamide phosphoribosyltransferase (NAMPT) showed upregulated expression in anaplastic meningiomas. However, targeting NAMPT to treat anaplastic meningiomas has not been reported. In vitro, NAMPT inhibitor -FK866 reduced the viability of anaplastic meningiomas by inducing cell cycle arrest at the G2/M phase. Intriguingly, the NAMPT inhibitor -FK866 decreased the protein expression of immune checkpoints PD-L1 and B7-H3 by down-regulating the STAT1 and p-STAT1 expression in vitro. Furthermore, FK866 suppressed the growth of anaplastic meningiomas in an in vivo xenograft model. The expression of Ki-67 and immune checkpoint proteins (PD-L1 and B7-H3) showed significant differences between the group treated with FK866 and the control group treated with DMSO. In conclusion, the expression of NAMPT, which plays a crucial role in energy metabolism, was upregulated in anaplastic meningiomas. The NAMPT inhibitor -FK866 significantly suppressed the growth of anaplastic meningiomas in vitro and in vivo. More strikingly, FK866 potently inhibited immune checkpoint protein (PD-L1 and B7-H3) expression by regulating STAT1 in vitro and in vivo. Our results demonstrated that NAMPT inhibitors could potentially be an effective treatment method for patients suffering from anaplastic meningiomas.

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.

The demand for high‐throughput and scalable cell expansion platforms that can accommodate diverse cell types remains a critical requirement across various biomedical fields. Fibronectin (Fn), an essential component of the extracellular matrix (ECM), has been used as a conformal surface coating for two‐dimensional (2D) cell culture systems. However, the soluble, globular Fn used for 2D coatings differs structurally from the native Fn, which possesses a three‐dimensional (3D) fibrillar structure. Herein, a large‐scale engineered ECM (EECM) cell expansion platform based on a 3D fibrillar Fn network spanning over centimeters is presented. Extended fibrillar networks are formed by shearing dilute Fn solutions over tessellated polymeric scaffolds, which are conveniently prepared by 3D printing. The structure and size of the Fn‐based 3D EECM scaffold are optimized by evaluating the proliferation of a colorectal tumor cell line, CT26, commonly used in the in vivo tumor immunotherapy models. The 3D EECM scaffolds support a fourfold more efficient tumor cell expansion than a conventional 2D culture system, demonstrating the potential efficacy in supporting the robust expansion of cancer cells ex vivo with an eye on cancer immunotherapy.

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