Dataset Information

Loss of p14 reduces immunogenicity in melanoma by affecting the peptide surface density via non-canonical Wnt signaling

ABSTRACT: CDKN2A and its two gene products p14 and p16 are one of the most frequently negatively altered gene loci (either by loss or mutation) in advanced melanoma accompanied by decreased T cell infiltration in melanoma. In this study, we shed light on the connection of the reduction of the CDKN2A gene product p14 and its impact on melanoma immunogenicity. Knockdown of p14 in melanoma cell lines diminishes the recognition and killing by melanoma differentiation antigen (MDA) specific T cells. Resistance was caused by a reduction of surface density of presented differentiation surface antigens. While antigen presentation via HLA-I molecules was enhanced upon p14 downregulation in general, absolute and relative expression of cognate peptides was decreased. Limiting Wnt5a signaling reverted this phenotype showing involvement of non-canonical Wnt signaling. Taken together, our data indicate a new mechanism limiting MDA specific T cell responses by decreasing both absolute and relative MDA-peptide presentation in melanoma.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Melanocyte, Cell Culture

DISEASE(S): Melanoma

SUBMITTER: Melissa Bernhardt

LAB HEAD: Andreas Schlosser

PROVIDER: PXD046891 | Pride | 2025-05-06

REPOSITORIES: Pride

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			Action	DRS
	2023-04-17_Fusion_36992.raw	Raw
	2023-04-17_Fusion_36993.raw	Raw
	2023-04-17_Fusion_36997.raw	Raw
	2023-04-17_Fusion_36998.raw	Raw
	2023-04-17_Fusion_37002.raw	Raw

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Publications

Loss of p14 diminishes immunogenicity in melanoma via non-canonical Wnt signaling by reducing the peptide surface density.

Wohlfarth Jonas J Kosnopfel Corinna C Faber Dominic D Berthold Marion M Siedel Claudia C Bernhardt Melissa M Schlosser Andreas A Aprati Tyler T Liu David D Schrama David D Houben Roland R Schadendorf Dirk D Goebeler Matthias M Meierjohann Svenja S Schilling Bastian B

Molecular oncology 20240528 10

Immunotherapy has achieved tremendous success in melanoma. However, only around 50% of advanced melanoma patients benefit from immunotherapy. Cyclin-dependent kinase inhibitor 2A (CDKN2A), encoding the two tumor-suppressor proteins p14ARF and p16INK4a, belongs to the most frequently inactivated gene loci in melanoma and leads to decreased T cell infiltration. While the role of p16INK4a has been extensively investigated, knowledge about p14ARF in melano ...[more]

PMID: 38807304

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