Immunoinformatic-Based Mapping of Cytotoxic T-Cell Epitopes of Overexpressed Proteins in Four High-mortality Cancers Determined Through Gene Expression Analysis

Background: Pancreatic, liver, colorectal, and lung cancer are some of the cancers with the highest mortality rates and the poorest prognosis. The discovery of cytotoxic T-cell (CD8+) epitopes in tumor-associated antigens (TAAs) common to these four types of cancer could lead to the development of potential multi-purpose vaccine constructs and formulations. Methods: Common overexpressed TAAs in the four deadliest cancer types were determined through gene expression analysis and the CD8+ epitopes were determined through immunoinformatics. The predicted epitopes were screened using multiple parameters measuring binding affinity and tendency to be presented by common human leukocyte antigen I (HLA I) alleles. They were also evaluated for antigenicity, allergenicity, toxicity, cross-reactivity, and population coverage. The epitope-HLA pairs were further analyzed for their interactions and binding affinity through molecular docking studies. Results: Integrin subunit alpha 2 (ITGA2), solute carrier family 2 member 1 (SLC2A1), and TPX2 microtubule nucleation factor (TPX2) were found to be significantly upregulated in 3 out of the 4 cancer types studied. Epitope mapping of ITGA2, SLC2A1, and TPX2 resulted in 12, 10, and 6 candidate CD8+ T-cell epitopes, respectively. Each set of epitopes from the 3 highly upregulated TAAs can cover wider population range, with ITGA2 covering the largest percentage, followed by TPX2 and lastly, by SLC2A1. Molecular docking analysis showed acceptable binding affinity between the epitope-HLA pairs. Conclusions: This is the first study to screen common highly upregulated TAAs found in different cancer types through gene expression analysis. Potentially immunogenic CD8+ epitopes were identified from ITGAX2, SLC2A1, and TPX2 through immunoinformatics. The epitopes, especially in combination, can cover wider population range where the deadliest cancer types are prevalent. Identified CD8+ epitopes can be included as potential multi-purpose agents in cancer immunotherapy against multiple deadly cancer types.