Frameshift peptide neoantigens from coding microsatellite insertion–deletion mutations in mismatch repair-deficient tumors (FSP neoantigens (from cMS indels in dMMR/MSI-H tumors))

Frameshift peptide neoantigens from coding microsatellite indels arise when mismatch repair deficiency causes insertion–deletion mutations in coding microsatellites, creating novel open reading frames that generate non-self peptides with high MHC class I binding potential and strong immunogenicity; these neoantigens are abundant in microsatellite instability-high tumors and are being developed as shared targets for vaccines, TCR-engineered T cells, and are indirectly leveraged by PD-1/PD-L1 checkpoint inhibitors, with MSI-H/dMMR serving as key predictive biomarkers for immunotherapy response.

Other names

Frameshift peptide neoantigensFrameshift neoantigensCoding microsatellite frameshift peptidesMicrosatellite instability-induced frameshift peptidesIndel-derived neoantigensShared frameshift neoantigens in MSI-H/dMMR cancers

Immune checkpoint blockade enabling T-cell responses against tumor neoantigens, including frameshift peptide neoantigens, via PD-1 inhibition. Therapeutic vaccination to prime T-cell immunity against shared frameshift peptide neoantigens. TCR-engineered T cells recognizing shared frameshift neoantigens.