Identification of an MSI-H Tumor-Specific Cytotoxic T Cell Epitope Generated by the (−1)‎ Frame of U79260(FTO)‎

Abstract EN

Microsatellite instability (MSI-H) induced by defects of the DNA mismatch repair system results in insertion or deletion of single nucleotides at short repetitive DNA sequences.

About 15% of sporadic and approximately 90% of hereditary nonpolyposis colorectal cancers display MSI-H.

When affecting coding regions, MSI-H results in frameshift mutations and expression of corresponding frameshift peptides (FSPs).

Functional tumor promoting relevance has been demonstrated for a growing number of genes frequently hit by MSI-H.

Contrary, immune reactions against FSPs are involved in the immune surveillance of MSI-H cancers.

Here, we provide conclusive data that the (−1) frame of U79260(FTO) encodes an HLA-A0201-restricted cytotoxic T cell epitope (FSP11; TLSPGWSAV).

T cells specific for FSP11 efficiently recognized HLA-A0201(pos) tumor cells harboring the mutated reading frame.

Considering the exceptionally high mutation rate of U79260(FTO) in MSI-H colorectal carcinoma (81.8%), this recommends that FSP11 be a component of future vaccines.