Intrinsic immune evasion patterns predict temozolomide sensitivity and immunotherapy response in lower-grade gliomas

Abstract

Abstract Background Although intrinsic immune-evasion is important in cancer proliferation, metastasis and response to treatment, it is unclear whether intrinsic immune-evasion patterns of gliomas can aid in predicting clinical prognosis and determining treatment. Methods A total of 182 immune-evasion genes intrinsic to cancer were subjected to consensus clustering to identify immune-evasion patterns in 1421 patients with lower-grade glioma (LGG). The levels of each cancer hallmark were determined by the Gene Set Variant Analysis (GSVA) method, and immune cell infiltrations were quantified using two algorithms, the single-sample Gene Set Enrichment Analysis (ssGSEA) and the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) methods. IEVscore was determined by a method that combined univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression and principal component analysis (PCA). Results Transcriptional and genomic analysis showed that most immune evasion genes (IEVGs) were upregulated in LGGs, with aberrant expression driven by alterations in copy number variants (CNV). Based on the mRNA expression profiles of cancer-intrinsic IEVGs could be divided into three LGG subgroups with distinct prognosis, clinicopathological features and immune infiltrations. A combined scoring scheme designed to assess the immune-evasion levels of LGGs divided these 1421 patients into two subgroups that differed in IEVscores. LGG patients with low-IEVscore had a better prognosis, would be more likely to benefit from immune check-point inhibitors and would be more susceptible to temozolomide (TMZ) chemotherapy. Conclusion Intrinsic immune evasion in the tumor microenvironment (TME) has a crucial effect on glioma formation. Quantitatively assessing the IEV scores of individual LGG patients could enhance knowledge about the intra-glioma microenvironment and lead to the development of individualized therapeutic strategies for patients with LGG.