Abstract
BackgroundTumor-infiltrating immune cells (TIICs) are highly relevant to clinical outcome of glioma. However, previous studies cannot account for the diverse functions that make up the immune response in malignant transformation (MT) from low-grade glioma (LGG) to high-grade glioma (HGG).MethodsTranscriptome level, genomic profiles and its relationship with clinical practice were obtained from TCGA and CGGA database. The “Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)” algorithm was used to estimate the fraction of 22 immune cell types. We divided the TCGA and CGGA set into an experiment set (n = 174) and a validation set (n = 74) by random number table method. Univariate and multivariate analyses were performed to evaluate the 22 TIICs’ value for MT in LGG. ROC curve was plotted to calculate area under curve (AUC) and cut-off value.ResultsHeterogeneity between TIICs exists in both intra- and inter-groups. Several TIICs are notably associated with tumor grade, molecular subtypes and survival. T follicular helper (TFH) cells, activated NK Cells and M0 macrophages were screened out to be independent predictors for MT in LGG and formed an immune risk score (IRS) (AUC = 0.732, p < 0.001, 95% CI 0.657–0.808 cut-off value = 0.191). In addition, the IRS model was validated by validation group, Immunohistochemistry (IHC) and functional enrichment analyses.ConclusionsThe proposed IRS model provides promising novel signatures for predicting MT from LGG to HGG and may bring a better design of glioma immunotherapy studies in years to come.
Highlights
Tumor-infiltrating immune cells (TIICs) are highly relevant to clinical outcome of glioma
The World Health Organization (WHO) classifies gliomas according to histology and molecular subtype, and grades them by the scale of I, II, III, IV. low-grade gliomas (LGG) typically range from grades I–II, while highgrade gliomas (HGG) are categorized as grades III–IV
Datasets We examined expression data and clinical variables from the following main sources: The Cancer Genome Atlas (TCGA) dataset,Chinese Glioma Genome Atlas (CGGA) dataset
Summary
Tumor-infiltrating immune cells (TIICs) are highly relevant to clinical outcome of glioma. Melanoma and non-small-cell lung cancer are the two solid tumors in which immunotherapy has proved to be effective [7]. Compared with these two tumors, glioma harbors a lower burden of somatic mutations and a more immunosuppressive tumor microenvironment [8]. Previous studies have revealed that glioblastomas are heavily infiltrated with monocytes/microglia, TIICs are relatively rare. Reports suggest that these cells account for 10–30% of viable cells within the tumor mass. While preclinical data shows the success of immunotherapy for gliomas, the profiles of TIICs in glioma and their clinical value still remain to be explained
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