Data from Multifactorial Remodeling of the Cancer Immunopeptidome by IFNγ

• DOI: 10.1158/2767-9764.c.6935964.v1
• Publication Date: 2023-11-17T14:20:34Z
• Authors: Alice Newey; Lu Yu; Louise J. Barber; Jyoti S. Choudhary; Michal Bassani-St...; Marco Gerlinger
• Keywords: Cancer Immunotherapy

<div>Abstract<p>IFNγ alters the immunopeptidome presented on HLA class I (HLA-I), and its activity cancer cells is known to be important for effective immunotherapy responses. We performed proteomic analyses of untreated IFNγ-treated colorectal patient-derived organoids combined this with transcriptomic HLA-I immunopeptidomics data dissect mechanisms that lead remodeling through IFNγ. IFNγ-induced changes in abundance source proteins, switching from constitutive immunoproteasome, differential upregulation different alleles explained some, but not all, observed peptide changes. By selecting peptides which increased or decreased most abundance, originated proteins limited changes, we discovered amino acid composition also influences whether a upregulated downregulated The presence proline within core was strongly associated downregulation. This validated an independent dataset. Proline substitution relevant positions did influence predicted binding affinity stability, indicating effects processing may relevant. Understanding multiple factors absence IFNγ identify best targets antigen-specific immunotherapies such as vaccines T-cell receptor engineered therapeutics.</p>Significance:<p>IFNγ remodels HLA-I–presented immunopeptidome. showed peptide-specific identified preferential loss downregulation those near center. will help target antigens are consistently by cells.</p></div>