Characterization of shared neoantigens in Endometrial Cancer with Microsatellite Instability

Abstract Endometrial cancer (EC) with microsatellite instability (MSI) are characterized by the accumulation of insertions/deletions at microsatellite sites, mainly mononucleotide repeats (MNRs). These MSI-related mutations lead to the synthesis of frameshift peptides (FSPs) that represent tumor-specific neoantigens (nAg) proved to be shared across patients/tumors with MSI. In this study we explored the feasibility of a nAg-based cancer vaccination design in EC with MSI. We adopted a whole exome sequencing approach and ad hoc bioinformatics pipelines to characterize FSPs in 35 patients with EC. A mean of 100 mutated MNRs was identified with an enrichment in patients’ group with MLH1 impairment. A high coverage emerged from the comparative analysis of the EC FSPs with the content of the previously validated NOUS-209 vaccine. We also obtained evidences of translation of EC FSPs as expressed proteins from Riboseq data, supporting the potential as target of vaccination. The development of a nAgs-based vaccine strategy in EC with MSI may be further explore. Cancer vaccination in combination with checkpoint inhibition could represent an enhancement of the immunotherapeutic approach in EC.