Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer

Endometrial cancer (EC) with Mismatch Repair deficiency (MMRd) is\r\ncharacterized by the accumulation of insertions/deletions at\r\nmicrosatellite sites. These mutations lead to the synthesis of\r\nframeshift peptides (FSPs) that represent tumor-specific neoantigens\r\n(nAg) proved to be shared across patients/tumors with MMRd. In this\r\nstudy, we explored the feasibility of a nAg-based cancer vaccination\r\ndesign in EC with MMRd. We adopted a whole exome sequencing approach and\r\nad hoc bioinformatics pipelines to characterize FSPs in 35 patients with\r\nEC. A mean of 146 mutated mononucleotide repeats (MNRs) was identified\r\nwith enrichment in the patients' group with MLH1 impairment. A high\r\ncoverage emerged from the comparative analysis of the EC FSPs with the\r\ncontent of the previously validated NOUS-209 vaccine. We obtained pieces\r\nof evidence of FSPs translation as expressed proteins from Ribo-seq,\r\nsupporting the potential as the target of vaccination. The development\r\nof a nAgs-based vaccine strategy in MMRd EC may be further explored.