Abstract
The use of vaccines for cancer therapy is a promising immunotherapeutic strategy that has been shown to be effective against various cancers. Vaccines directly target tumors but their efficacy against glioblastoma multiforme (GBM) remains unclear. Immunotyping that classifies tumor samples is considered to be a biomarker for immunotherapy. This study aimed to identify potential GBM antigens suitable for vaccine development and develop a tool to predict the response of GBM patients to vaccination based on the immunotype. Gene Expression Profiling Interactive Analysis (GEPIA) was applied to evaluate the expression profile of GBM antigens and their influence on clinical prognosis, while the cBioPortal program was utilized to integrate and analyze genetic alterations. The correlation between antigens and antigen processing cells was assessed using TIMER. RNA-seq data of GBM samples and their corresponding clinical data were downloaded from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) for further clustering analysis. Six overexpressed and mutated tumor antigens (ARHGAP9, ARHGAP30, CLEC7A, MAN2B1, ARPC1B and PLB1) were highly correlated with the survival rate of GBM patients and the infiltration of antigen presenting cells in GBMs. With distinct cellular and molecular characteristics, three immune subtypes (IS1-IS3) of GBMs were identified and GBMs from IS3 subtype were more likely to benefit from vaccination. Through graph learning-based dimensional reduction, immune landscape was depicted and revealed the existence of heterogeneity among individual GBM patients. Finally, WGCNA can identify potential vaccination biomarkers by clustering immune related genes. In summary, the six tumor antigens are potential targets for developing anti-GBMs mRNA vaccine, and the immunotypes can be used for evaluating vaccination response.
Highlights
Gliomas are intrinsic brain tumors arising from glial or precursor cells
We analyzed the immune status of glioblastoma multiforme (GBM) and identified patients likely to benefit from vaccination by conducting immunotyping
Several immunosuppressive factors such as TGF-b and IL-10 released by GBM cells, Tregs, microglia, macrophages, lead to local immunosuppression [75, 76]. These results indicated that GBMs of the IS3 subtype were more likely to benefit from vaccination in combination with immune checkpoint blockage
Summary
Gliomas are intrinsic brain tumors arising from glial or precursor cells. They are classified into grades I to grade IV based on the degree of undifferentiation, anaplasia, and aggressiveness [1]. Glioblastoma multiforme (GBM, grade IV glioma) accounts for 82% of all malignant gliomas and is characterized histologically by considerable vascular proliferation, cellularity and mitotic activity, and necrosis [2]. Despite the availability of standard treatment options for GBM including surgical resection, radiotherapy and chemotherapy, the median survival time of GBM patients is only 12–15 months after diagnosis [3, 4]. Several studies have explored the efficacy of immunotherapy in the treatment of glioblastoma [5]
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