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Desthiobiotin-Streptavidin-Affinity Mediated Purification of RNA-Interacting Proteins in Mesothelioma Cells
Published on: April 25, 2018
Identification of Potential Antigens for Developing mRNA Vaccine for Immunologically Cold Mesothelioma
Shichao Zhang1, Shuqin Li1, Ya Wei1
1Key Laboratory of Infectious Immune and Antibody Engineering in Guizhou Province, School of Biology and Engineering, Guizhou Medical University, Guiyang, China.
Abstract:
Messenger RNA vaccines are considered to be a promising strategy in cancer immunotherapy, while their application on mesothelioma is still largely uncharacterized. This study aimed to identify potential antigens in mesothelioma for anti-mesothelioma mRNA vaccine development, and further determine the immune subtypes of mesothelioma for selection of suitable candidates from an extremely heterogeneous population. Gene expression data and corresponding clinicopathological information were obtained from the TCGA and gene expression omnibus, respectively. Then, the genetic alterations were compared and visualized using cBioPortal, and differentially expressed genes and their prognostic signatures were identified by GEPIA. The relationship between tumor-infiltrating immune cells and the expression of tumor antigens was systematically evaluated by TIMER online. Finally, the immune subtypes and immune landscape of mesothelioma were separately analyzed using consensus cluster and graph learning-based dimensional reduction. A total of five potential tumor antigens correlated with prognosis and infiltration of antigen-presenting cells, including AUNIP, FANCI, LASP1, PSMD8, and XPO5 were identified. Based on the expression of immune-related genes, patients with mesothelioma were divided into two immune subtypes (IS1 and IS2). Each subtype exhibited differential molecular, cellular and clinical properties. Patients with the IS1 subtype were characterized by an immune "cold" phenotype, displaying superior survival outcomes, whereas those with the IS2 subtype were characterized by an immune "hot" and immunosuppressive phenotype. Furthermore, immune checkpoints and immunogenic cell death modulators were differentially expressed between the IS1 and IS2 immune subtype tumors. The immunogenomic landscape of mesothelioma revealed a complex tumor immune microenvironment between individual patients. AUNIP, FANCI, LASP1, PSMD8, and XPO5 are putative antigens for the development of anti-mesothelioma mRNA vaccine and patients with the IS1 subtype may be considered for vaccination.
Insights
Researchers identified five potential tumor antigens (AUNIP, FANCI, LASP1, PSMD8, XPO5) for mesothelioma mRNA vaccines. Mesothelioma patients were classified into two immune subtypes, with one showing a cold, favorable phenotype potentially suitable for vaccination.
Area of Science:
- Oncology
- Immunology
- Vaccine Development
Background:
- Mesothelioma immunotherapy using mRNA vaccines is under-explored.
- Mesothelioma is a highly heterogeneous cancer, necessitating personalized treatment strategies.
Purpose of the Study:
- To identify potential tumor antigens for anti-mesothelioma mRNA vaccine development.
- To classify mesothelioma into immune subtypes for targeted vaccine candidate selection.
Main Methods:
- Utilized TCGA and GEO datasets for gene expression and clinicopathological data.
- Employed cBioPortal, GEPIA, and TIMER for genetic alteration analysis, differential gene expression, and immune cell infiltration assessment.
- Applied consensus clustering and graph learning for immune subtype and landscape analysis.
Main Results:
- Identified five prognostic tumor antigens (AUNIP, FANCI, LASP1, PSMD8, XPO5) associated with antigen-presenting cell infiltration.
- Classified mesothelioma patients into two distinct immune subtypes (IS1 and IS2) with differing molecular, cellular, and clinical characteristics.
- IS1 subtype: immune-cold phenotype, better survival. IS2 subtype: immune-hot, immunosuppressive phenotype, differential expression of immune checkpoints and immunogenic cell death modulators.
Conclusions:
- AUNIP, FANCI, LASP1, PSMD8, and XPO5 are promising antigens for mesothelioma mRNA vaccine development.
- The IS1 immune subtype, characterized by an immune-cold phenotype, may be a suitable candidate population for mRNA vaccination in mesothelioma.
