Association of IDH mutation and 1p19q co-deletion with tumor immune microenvironment in lower-grade glioma

Although the successful clinical trials of immunotherapy show promising strategies for many cancers, its application in glioma has lagged in comparison with the progress seen in other cancers. Both isocitrate dehydrogenase (IDH) mutations and 1p/19q codeletions are critical molecular alterations affecting therapeutic response in lower-grade glioma (LGG). The systematic and comprehensive characterization of the immunological phenotypes with different molecular subtypes is key to improving our understanding and application of immunotherapies in LGG. Here, we collected the RNA-sequencing, somatic mutation, and clinical data from 1,052 patients from The Cancer Genome Atlas and Chinese Glioma Genome Atlas and stratified patients into three genetic subgroups: IDH mutations with 1p/19q codeletions (IDH mut-codel), IDH mutations without 1p/19q codeletions (IDH mut-noncodel), and IDH wild-type. Our evaluations revealed that IDH mutations and 1p/19q codeletions were associated with distinct immunological tumor microenvironments in LGG. In addition, immune cell infiltration, the expression of immune checkpoint and human leukocyte antigen (HLA) gene, and the activity of immune signaling pathways shared gradual increase from IDH mut-co-del to IDH wild-type. We further constructed and validated an immune-related prognostic signature that presented high value in predicting the overall survival time in LGG. In conclusion, our study may provide valuable information for immunotherapy strategies in LGG patients.

Automated summary

While successful clinical trials of immunotherapy have shown promising strategies for many cancers, its application in glioma has lagged behind compared to other cancers. This study focused on the molecular alterations affecting therapeutic response in lower-grade glioma (LGG) and characterized the immunological phenotypes with different molecular subtypes to improve our understanding and application of immunotherapies in LGG. The research collected data from 1,052 patients, stratified them into three genetic subgroups, and discovered distinct immunological tumor microenvironments associated with IDH mutations and 1p/19q codeletions in LGG, ultimately leading to the construction of an immune-related prognostic signature that predicts overall survival time in LGG.