ArticleMolecular & cellular oncology2025
The immunopeptidome of colon cancer cells treated with topoisomerase inhibiting drug reveals differential as well as common endogenous protein sampling and display of MHC I-associated peptides.
Article in Molecular & cellular oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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6 authors.
Funding
Abstract
Immunotherapy options for microsatellite stable (MSS) colorectal cancer are currently very limited. The lack of detectably unique or altered immunogens in the tumor microenvironment may be a factor. Radiation and chemotherapy may enhance immunotherapy by increasing cancer cell visibility through Major Histocompatibility Complex I (MHC I) expression. To investigate this, we treated MSS and microsatellite-instable (MSI) colon cancer cells with a topoisomerase inhibitor and analyzed MHC I-associated peptides. Treatment increased peptide numbers by 5% in RKO (MSI) cells and 83% in SW620 (MSS) cells, with 40-50% of peptides being exclusive to treatment. Additionally, clustering analysis revealed a set of peptides with uniquely conserved residues displayed only in treated MSS SW620 cells. Gene Ontology analysis of MHC I-displayed proteins revealed a treatment-induced increase in extracellular vesicle- and nuclear-derived proteins, alongside reduced cytosolic protein sampling. Overall, we present evidence for treatment-inducible differential display of peptides, some of which may affect interactions and functions of immune cells. Given the multitude of factors that modulate the effects of increased MHC I expression and associated peptides, further studies are needed to elucidate the pathophysiological implications of these changes.
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