PXD076097

PXD076097 is an original dataset announced via ProteomeXchange.

Title	The transmembrane IL-15 isoform expressed on human melanoma cells triggers modulatory effects on tumor progression upon stimulation with the soluble IL-15R chain
Description	Interleukin-15 (IL-15) is expressed in various cancers, including melanoma, where it exists in distinct membrane-associated isoforms. Primary melanoma cells predominantly express the non-cleavable transmembrane form (tmbIL-15), while metastatic cells also express a cleavable membrane-bound form (mbIL-15) complexed with IL-15Rα. As tmbIL-15 is capable of reverse signaling upon IL-15Rα engagement, we investigated how this signaling axis modulates melanoma cell behavior across tumor stages. Transcriptomic analysis of melanoma patients revealed that high IL-15 expression correlates with immune activation, inflammation and epithelial-to-mesenchymal transition (EMT), along with coordinated upregulation of IL-15 receptor subunits. Proteomic profiling of melanoma cell lines stimulated with soluble IL-15Rα (sIL-15Rα) uncovered distinct, stage-specific responses. Although several proteins were commonly deregulated across cell lines, most showed opposite regulation in primary versus metastatic models, indicating that tmbIL-15 reverse signaling triggers context-dependent programs influenced by tumor progression. A stringent cross-comparison identified five proteins (PSAP, MARCKS, eEF1A1, DDX39B, and RACK1) as consistently and differentially regulated across tumor stages. Further comparison with published NK cell co-culture and EMT cytokine stimulation datasets revealed a subset of shared effectors, notably PSAP, TPM3 isoform 2 and MARCKS, suggesting that IL-15Rα–induced tmbIL-15 signaling is part of the immune editing phenomenon eliciting pro-tumoral activities complementary to the EMT process. 61 Among these, PSAP emerged as the most robustly and consistently modulated effector, upregulated in primary melanoma cells and downregulated in metastatic ones upon sIL-15Rα stimulation. Its expression correlated positively with CD8+ T cell infiltration and negatively with NK cell infiltration, with distinct transcriptomic programs associated with high PSAP expression in primary versus metastatic settings. Altogether, these findings identify PSAP as a stage-specific mediator of tmbIL-15 reverse signaling in melanoma, integrating immune and EMT-related cues with potential implications for tumor progression and microenvironmental remodeling.
HostingRepository	PRIDE
AnnounceDate	2026-05-25
AnnouncementXML	Submission_2026-05-24_16:14:39.804.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maria Concetta Cufaro
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-24 14:06:26	ID requested
⏵ 1	2026-05-24 16:14:40	announced

Forcelloni S, Giron-Michel J, Del Boccio P, Cufaro MC, Di Sebastiano A, Mariotti FR, Ciancaglini C, Chouaib S, Padelli M, Vespa S, Mac GD, Ebert S, Buart S, Maggi E, Moretta L, Vacca P, Tumino N, Quatrini L, Caruana I, Azzarone B, Santopolo S, chain. Front Immunol, 17():1798481(2026) [pubmed]

10.3389/fimmu.2026.1798481;

submitter keyword: IL15,Cytokine, IL15Rα, Skin Cancer (melanoma), Natural killer (NK) cells

Piero Del Boccio
contact affiliation	Department of Science, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy
contact email	piero.delboccio@unich.it
lab head
Maria Concetta Cufaro
contact affiliation	University "G. d'Annunzio" of Chieti
contact email	maria.cufaro@unich.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD076097

PRIDE project URI

• PRIDE
  1. PXD076097
     1. Label: PRIDE project
     2. Name: The transmembrane IL-15 isoform expressed on human melanoma cells triggers modulatory effects on tumor progression upon stimulation with the soluble IL-15R chain