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Published on: September 25, 2011
Identification of neoantigen epitopes in cervical cancer by multi-omics analysis
Jing Yuan1,2,3, Na Xu1,2,3, Xueqi Gong1,2,3
1Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background:
Tumor vaccines enhance the immune response and cytotoxicity of tumor-specific T cells and show promising clinical therapeutic efficacy. Although most cervical cancer cells express HPV-related oncoproteins, some do not. Additionally, neoantigens worth attracting attention for cervical cancer (CC) may hold the potential for breakthroughs in the development of cervical cancer vaccines.
Methods:
A comprehensive computational analysis was conducted based on the tumor genome, transcriptome, and proteome data from 284 cervical cancer samples obtained from the TCGA database. Frequently mutated genes were identified. The levels of immune cell infiltration were analyzed using RNA-seq data, high-frequency mutated genes were identified as candidate genes that were significantly related to immune infiltration. Focusing on MHC class I epitopes recognized by CD8 + T cells, we predicted potential neoantigen peptides using the NetMHCpan-4.0 and NetCTL-1.2 algorithms. To further confirm the immunogenicity of the synthesized peptides, we performed flow cytometry and real-time PCR in vivo to examine markers of T cell activation and cytotoxicity. We also stimulated PBMC from patients with the corresponding HLA type with the synthesized peptides using an ELISpot assay.
Results:
We identified 30 highly mutated genes, among which TTN, PRKDC, PCLO, MUC17, HUWE1, RYR2, and CREBBP positively correlated with immune cell infiltration into the tumor microenvironment. PCLO exhibited higher protein expression in tumor tissues than in the corresponding normal tissues, making it a potential tumor antigen. The PCLO peptides SISRFTLEK and LSEAGHFFY exhibited the highest predicted scores among the cancer antigens and strong immunogenicity in vivo.
Conclusion:
Our analysis highlights the potential of PCLO as a candidate gene for enhancing immune cell infiltration and activating immune responses in tumors. The peptides SISRFTLEK (PCLOL4169F) and LSEAGHFFY (PCLOA3000S) are promising targets for tumor vaccines.
Insights
This study identifies PCLO as a promising target for cervical cancer vaccines. Specific PCLO peptides show strong immunogenicity, enhancing immune cell infiltration and activation for potential therapeutic breakthroughs.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Cervical cancer (CC) vaccines aim to enhance anti-tumor immunity, but not all CC cells express HPV oncoproteins.
- Identifying novel neoantigens is crucial for advancing CC vaccine development.
Purpose of the Study:
- To computationally analyze cervical cancer data to identify potential neoantigens for vaccine development.
- To evaluate the immunogenicity of identified neoantigen candidates.
Main Methods:
- Comprehensive analysis of genomic, transcriptomic, and proteomic data from 284 CC samples.
- Identification of frequently mutated genes correlated with immune cell infiltration.
- Prediction and in vivo validation of MHC class I epitopes and neoantigen peptides.
Main Results:
- Thirty highly mutated genes were identified; PCLO showed significant correlation with immune cell infiltration and higher protein expression in tumors.
- PCLO peptides SISRFTLEK and LSEAGHFFY demonstrated high predicted scores and strong in vivo immunogenicity.
- These peptides are potential tumor antigens for cervical cancer.
Conclusions:
- PCLO is a promising candidate gene for improving immune cell infiltration and response in cervical tumors.
- The PCLO-derived peptides SISRFTLEK and LSEAGHFFY represent potential therapeutic targets for cervical cancer vaccines.
