Abstract
Objective Low-grade glioma (LGG) mainly threatens the elderly population, with undesirable prognoses. This study uncovered the immune cell infiltration (ICI) landscape in LGG. Methods RNA-seq profiles of LGG were retrieved from TCGA and CGGA databases. CIBERSORTx and ESTIMATE algorithms were employed to characterize the ICI landscape in LGG tissues. Through unsupervised clustering analysis, ICI subtypes were clustered. ICI scores were computed via principal component analysis (PCA). The differences in survival, tumor-infiltrating immune cells, stromal scores, immune scores, immune checkpoint genes, immune activity genes, and tumor mutation burden (TMB) were assessed between high and low ICI score groups. Results Three ICI subtypes were constructed in LGG, with distinct survival outcomes, PD-L1 expression, and infiltration levels of immune cells. Furthermore, ICI scores were developed. Both in TCGA and CGGA datasets, low ICI scores were indicative of undesirable outcomes. High ICI scores were significantly correlated to increased infiltration levels of memory B cells, CD8 T cells, CD4 naïve T cells, T follicular helper cells, macrophages M0, and eosinophils, while low ICI scores were characterized by increased infiltration levels of naïve B cells, plasma cells, CD4 memory resting T cells, Tregs, resting NK cells, macrophages M2, and activated dendritic cells. High ICI scores exhibited correlations with lower immune activity genes and immune checkpoint genes. Furthermore, TMB was distinctly reduced in the high ICI score group. Conclusion The ICI scores may serve as a promising prognostic index and predictive indicator for immunotherapies, extending our understanding of immune microenvironment in LGG.
Highlights
Glioma is a common primary intracranial malignancy, which is classified into four grades according to the 2007 WHO classification of tumors: Grades I and II are LGGs, and Grades III and IV are high-grade gliomas [1]
The CIBERSORTx and ESTIMATE algorithms were employed for determining the infiltration levels of immune cells in LGG tissues
principal component analysis (PCA) results confirmed the distinct classifications into three subtypes: ICI subtype A (n 245), ICI subtype B (n 75), and ICI subtype C (n 186; Figure 1(d))
Summary
Glioma is a common primary intracranial malignancy, which is classified into four grades according to the 2007 WHO classification of tumors: Grades I and II are LGGs, and Grades III and IV are high-grade gliomas [1]. LGG represents the most common primary brain malignancy [2]. It is predisposed to younger individuals (average age: 41 years old), with mean survival time of approximately seven years [3]. Despite the much progress in neurosurgical resection, chemotherapy, and radiotherapy, it is ineluctable to experience resistance and recurrence [4]. Some subjects experience indolent outcomes, while others develop into high-grade gliomas with undesirable outcomes [5]. Despite the less aggressiveness of LGG, patients usually have varied survival outcomes [6]. Despite the less aggressiveness of LGG, patients usually have varied survival outcomes [6]. erefore, discovering precisely novel markers to predict patients’ prognosis is of importance in current studies
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