Antigen Presentation Machinery Signature-Derived CALR Mediates Migration, Polarization of Macrophages in Glioma and Predicts Immunotherapy Response

Immunogenicity, influenced by tumor antigenicity and antigen presenting efficiency, critically determines the effectiveness of immune checkpoint inhibitors. The role of immunogenicity has not been fully elucidated in gliomas. In this study, a large-scale bioinformatics analysis was performed to analyze the prognostic value and predictive value of antigen presentation machinery (APM) signature in gliomas. ssGSEA algorithm was used for development of APM signature and LASSO regression analysis was used for construction of APM signature-based risk score. APM signature and risk score showed favorable performance in stratifying survival and predicting tumorigenic factors of glioma patients. APM signature and risk score were also associated with different genomic features in both training cohort TCGA and validating cohort CGGA. Furthermore, APM signature-based risk score was independently validated in three external cohorts and managed to predict immunotherapy response. A prognostic nomogram was constructed based on risk score. Risk score-derived CALR was found to mediate the invasion and polarization of macrophages based on the coculture of HMC3 and U251 cells. CALR could significantly predict immunotherapy response. In conclusion, APM signature and APM signature-based risk score could help promote the clinical management of gliomas.