Author: ["Thorbald van Hall","Elisabeth Z Wolpert","Peter van Veelen","Sandra Laban","Michael van der Veer","Marjet Roseboom","Sandra Bres","Per Grufman","Arnoud de Ru","Hugo Meiring","Ad de Jong","Kees Franken","Antoinette Teixeira","Rob Valentijn","Jan Wouter Drijfhout","Frits Koning","Marcel Camps","Ferry Ossendorp","Klas Kärre","Hans-Gustaf Ljunggren","Cornelis J M Melief","Rienk Offringa"]
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Abstract
Defects in major histocompatibility complex (MHC) class I–restricted antigen presentation are frequently observed in human cancers and result in escape of tumors from cytotoxic T lymphocyte (CTL) immune surveillance in mice. Here, we show the existence of a unique category of CTLs that can prevent this escape. The CTLs target an alternative repertoire of peptide epitopes that emerge in MHC class I at the surface of cells with impaired function of transporter associated with antigen processing (TAP), tapasin or the proteasome. These peptides, although derived from self antigens such as the commonly expressed Lass5 protein (also known as Trh4), are not presented by normal cells. This explains why they act as immunogenic neoantigens. The newly discovered epitopes can be exploited for immune intervention against processing-deficient tumors through adoptive T-cell transfer or peptide vaccination.Cite this article
van Hall, T., Wolpert, E., van Veelen, P. et al. Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants. Nat Med 12, 417–424 (2006). https://doi.org/10.1038/nm1381 