Carboxypeptidase Q(CPQ) promotes glioma progression by inducing M2 macrophage polarization and immunosuppression.

BACKGROUND: The tumor microenvironment (TME) is immunosuppressive due to the high presence of tumor-associated macrophages (TAMs). Among the different macrophage phenotypes, M2 macrophages, which are typically associated with tissue repair and immune suppression, are often the predominant form within the TME. This environment is essential for the growth and advancement of glioma. In this study, we explored whether Carboxypeptidase Q (CPQ) plays a crucial role in immune regulation of glioma by driving polarization and recruitment of M2 macrophages. METHODS: Molecular and clinical data were derived from The Cancer Genome Altas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were utilized to predict the potential biological functions of CPQ. Single-cell analysis was utilized to identify the specific cell types expressing CPQ. The GSVA algorithm was employed to calculate the activity of immune suppression signaling pathways, while the CIBERSORT algorithm was used to quantify the infiltration of immune cells. The GSEA algorithm was utilized to analyze signal pathways between CPQ high- and low-expressing groups. Human glioma specimens were collected and CPQ expression was evaluated using immunofluorescence analysis. RESULTS: CPQ was linked to immune suppression in glioma. Elevated expression of CPQ was correlated with the increased expression of immunosuppressive checkpoints, such as PD-1, TIM-3, and CTLA-4. CPQ served as an effective gene for M2 macrophage polarization and recruitment. Furthermore, it could increase radiation resistance and operate as an independent marker of poor prognosis for glioma. CONCLUSION: CPQ was implicated in immunosuppressive activities, and its elevated expression was associated with increased radiation resistance. Furthermore, CPQ served as an independent adverse prognostic biomarker for patients with glioma.