LINE-1 ORF1p is a Shared and Immunogenic Antigen in Cancer

LINE-1 elements are normally repressed genomic sequences that can be reactivated in cancer. We demonstrate that ORF1p, a protein encoded by LINE-1, is selectively expressed in tumors and its peptides are presented on MHC class I molecules across diverse tumor types.

Using public and newly generated immunopeptidomics datasets, we detect ORF1p-derived peptides in a tumor-specific manner. Functional assays confirm that these peptides can elicit IFN-γ responses from CD4+ and CD8+ T cells in vitro. These findings highlight ORF1p as a promising candidate for a broadly applicable cancer vaccine.