Loss of ribosomal protein uL14 enables tumor escape from T cell immunosurveillance

The presentation of peptides on HLA molecules is essential to CD8<sup>+</sup> T cell responses. Here, we show that loss of uL14 significantly downregulates the expression of antigen processing and presentation (APP) components in melanoma cell lines. Peptides generated following knockdown show different characteristics, with altered peptide charge, and differences in anchor residue positions. These peptides also have lower predicted binding to the HLA alleles and a shorter predicted HLA-peptide complex half-life. These result in a functional difference in APP, and knockdown of uL14 causes a reduction in the ability of CD8<sup>+</sup> T cells to recognize and kill melanoma cells in a co-culture assay. Together, our data suggest that loss of uL14 alters the peptide pool available for presentation and thus may act as an escape mechanism from tumor immune surveillance.

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Publication Details

Journal
NAR Cancer
Published
2025-08-07
DOI
https://doi.org/10.1093/narcan/zcaf024
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
0.00

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article

Loss of ribosomal protein uL14 enables tumor escape from T cell immunosurveillance

Rob van der Kammen, Edwin Sakyi Kyei-Baffour, Ferhat Alkan, Pia Kvistborg et al.
NAR Cancer
CAR-T cell therapy research
article

Loss of ribosomal protein uL14 enables tumor escape from T cell immunosurveillance

Rob van der Kammen, Edwin Sakyi Kyei-Baffour, Ferhat Alkan, Pia Kvistborg, Maarten Altelaar, Yuval Malka, Kelly Hoefakker, William J. Faller, Onno B. Bleijerveld, Liesbeth Hoekman, Anna Dopler, Antonia Bradaric, Jonathan W. Yewdell, M.A.T. Kerkhoff
article en

Abstract

The presentation of peptides on HLA molecules is essential to CD8<sup>+</sup> T cell responses. Here, we show that loss of uL14 significantly downregulates the expression of antigen processing and presentation (APP) components in melanoma cell lines. Peptides generated following knockdown show different characteristics, with altered peptide charge, and differences in anchor residue positions. These peptides also have lower predicted binding to the HLA alleles and a shorter predicted HLA-peptide complex half-life. These result in a functional difference in APP, and knockdown of uL14 causes a reduction in the ability of CD8<sup>+</sup> T cells to recognize and kill melanoma cells in a co-culture assay. Together, our data suggest that loss of uL14 alters the peptide pool available for presentation and thus may act as an escape mechanism from tumor immune surveillance.

NAR CancerVol. 7(3)
Utrecht University (NL), University of Bristol (GB), Oncode Institute (NL), Pharmo Institute (NL), Cancer Genomics Centre (NL), National Institute of Allergy and Infectious Diseases (US)
Mark Foundation For Cancer Research, Ministerie van Volksgezondheid, Welzijn en Sport, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Knight-Wallace Fellows, University of Michigan
Openalex Percentile: Top 68%
CAR-T cell therapy research
DOIOpen Access PDFOpenAlex
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