Identification of Tumor Antigens and Immune Subtypes of Glioblastoma for mRNA Vaccine Development

Han Lin; Kun Wang; Yuxin Xiong; Liting Zhou; Yong Yang; Shanwei Chen; Peihong Xu; Yujun Zhou; Rui Mao; Guangzhao Lv; Peng Wang; Dong Zhou

doi:10.3389/fimmu.2022.773264

Identification of Tumor Antigens and Immune Subtypes of Glioblastoma for mRNA Vaccine Development

Front Immunol. 2022 Feb 2:13:773264. doi: 10.3389/fimmu.2022.773264. eCollection 2022.

Authors

Han Lin^{1

2}, Kun Wang³, Yuxin Xiong⁴, Liting Zhou⁵, Yong Yang¹, Shanwei Chen^{1

6}, Peihong Xu^{1

6}, Yujun Zhou^{1

7}, Rui Mao^{1

8}, Guangzhao Lv^{1

6}, Peng Wang¹, Dong Zhou¹

Affiliations

¹ Department of Neurosurgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
² Department of Head and Neck Surgery, Cancer Hospital of Shantou University Medical College, Shantou, China.
³ Department of Neurosurgery, The First Affiliated Hospital, Jinan University, Guangzhou, China.
⁴ Division of Vascular Intervention Radiology, The Third Affiliated Hospital of Sun Yet-Sen University, Guangzhou, China.
⁵ International Department, Affiliated High School of South China Normal University, Guangzhou, China.
⁶ Shantou University Medical College, Shantou, China.
⁷ Southern Medical University, Guangzhou, China.
⁸ School of Medicine, South China University of Technology, Guangzhou, China.

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.

Keywords: WGCNA; glioblastoma; immunotyping; landscape; mRNA vaccine; tumor immune microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Neoplasm / genetics*
Antigens, Neoplasm / immunology
Biomarkers, Tumor / genetics*
Brain Neoplasms / genetics*
Brain Neoplasms / immunology
Cancer Vaccines / immunology
Databases, Genetic
Gene Expression Profiling / methods*
Gene Expression Regulation, Neoplastic
Glioblastoma / genetics*
Glioblastoma / immunology
Humans
Immunophenotyping
Mutation
Prognosis
Tumor Microenvironment
Vaccine Development
Vaccines, Synthetic / immunology
mRNA Vaccines / immunology

Substances

Antigens, Neoplasm
Biomarkers, Tumor
Cancer Vaccines
Vaccines, Synthetic
mRNA Vaccines