PXD059186

PXD059186 is an original dataset announced via ProteomeXchange.

Title	Integration of functional precision oncology testing defines immunotherapies strategies for mucosal melanomas.
Description	Mucosal melanomas (MM) arise from mucosal melanocytes at different anatomical sites. MM are rare and highly aggressive, and their outcome is very poor.  Only dismal clinical benefits have been obtained for the disseminated disease, with very limited promising results using approved immune checkpoint inhibitors. Compared to the cutaneous counterpart, data on the immunogenicity and IFN-γ sensitivity of MM are largely missing. Here, we explored these issues combining microscopy and -omics approaches on a set of unique sino-nasal melanoma (SN-MM) cell lines and clinical samples.  All SN-MM cell lines display normal surface expression of IFNGR along with integrity of the IFNGR/JAK/STAT signaling pathway. Moreover, as a group, all SN-MM cell lines resulted responsive to the administration of IFN-γ as measured by transcriptomic and proteomic signatures. Specifically, IFN-γ induced canonical IFN-γ regulated genes involved in immune cell recognition and antigen presentation. In sixty percent of SN-MM cell lines IFN-γ also exerted a direct cytotoxic and anti-proliferative effect, release of CXCL10 and surface expression of CD274/PD-L1; the remaining fraction of SN-MM cell lines display IFN-γ functional refractoriness, likely dependent on post-transcriptional regulation of the IFN-γ regulated molecules. Analysis of clinical samples revealed that SN-MM are immune desert with scarce tumor-infiltrating lymphocytes (TILs), a feature predicting unfavourable outcomes; moreover, they resulted negative for CD274/PD-L1. This set of findings indicates that integration of functional precision oncology might refine the characterization of immune escape mechanisms to better allocate melanoma patients to various IT options.
HostingRepository	PRIDE
AnnounceDate	2026-03-16
AnnouncementXML	Submission_2026-03-16_04:05:50.975.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcello Manfredi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-23 05:51:32	ID requested
⏵ 1	2026-03-16 04:05:52	announced

10.1136/jitc-2025-012222;

Monti M, Picinoli S, Bozzola A, Ferrari M, Bugatti M, Pezzali I, Carlomagno M, Carta G, Orlandi M, Lora G, Benerini Gatta L, Missale F, Ferrari G, Baldazzi V, Rezzola S, Tabellini G, Parolini S, Manfredi M, De Giorgis V, Marengo E, Turri-Zanoni M, Nicolai P, Consoli F, Lombardi D, Martini P, Li J, Griffith O, Griffith M, Rossato M, Vermi W, Integrating interferon gamma receptor pathways, antigenicity, and immune contexture as predictors of immunotherapeutic strategies for mucosal melanomas. J Immunother Cancer, 14(3):(2026) [pubmed]

submitter keyword: proteomics, IFNgamma,Mucosal melanoma

Marcello Manfredi
contact affiliation	Università del Piemonte Orientale, Dipartimento di medicina traslazionale.
contact email	marcello.manfredi@uniupo.it
lab head
Marcello Manfredi
contact affiliation	University of Eastern Piedmont
contact email	marcello.manfredi@uniupo.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059186
     1. Label: PRIDE project
     2. Name: Integration of functional precision oncology testing defines immunotherapies strategies for mucosal melanomas.