PTX3 Mediates the Infiltration, Migration, and M2-Polarization of Macrophages in Glioblastoma by Large-Scale Single Cell Sequencing Analysis and in vitro Experiments

Background: Pentraxin 3 (PTX3) is an important regulator in the immune system. However, the immune modulatory role of PTX3 in tumor microenvironment of glioma has not been elucidated. Methods: The RNA seq samples were obtained from the Cancer Genome Atlas (TCGA) dataset and the China Glioma Genome Atlas (CGGA) dataset. The single cell sequencing data of glioblastoma (GBM) samples were obtained from the Single Cell Portal platform (http://singlecell.broadinstitute.org). Immunohistochemistry was used to assess the expression of PTX3, HAVCR2, PD-1, PD-L1, and CD276 in glioma sections from Xiangya cohort (n=60). Multiplex immunofluorescence staining of PTX3, CD68, and CD163 was performed in several solid cancer types including GBM. HMC3 was cocultured with U251, which transwell assay and flow cytometry assay were performed for HMC3.Findings: PTX3 expression is significantly increased in glioblastoma (GBM). PTX3 expression predicts worse survival in Xiangya cohort. PTX3 is closely related to the expression of PD-1, PD-L1, CD276, HAVCR2 in the tumor microenvironment. Additionally, PTX3 is involved in tumorigenic and immunogenic processes, especially the activity of macrophages based on various signaling pathways in cellular communications and critical transcription factors. PTX3 also actively participates in mediating the infiltration, migration, M2-polarization of macrophage through complex cellular communications and transcription factors.Interpretation: PTX3 is critically involved in the infiltration, migration, M2-polarization of macrophage and modulates an immunosuppressive microenvironment. Funding Information: National Natural Science Foundation of China, China Postdoctoral Science Foundation, Hunan Provincial Natural Science Foundation of China, Hunan Provincial Health Committee Foundation of China, Xiangya Hospital Central South University Postdoctoral Foundation.Declaration of Interests: All authors declare that they have no competing interests.