{
  "abstract": "Mucosal melanoma is a rare, lethal melanoma subtype with distinct genetics and limited benefit from immunotherapy. To define features associated with mucosal melanoma clinical outcomes, we assembled a large, multimodally profiled cohort spanning primary and metastatic disease. Compared with cutaneous melanoma, primary mucosal melanoma showed greater genomic heterogeneity, ploidy and aneuploidy, and a more dedifferentiated, proliferative transcriptional state. Analysis of genomic sequencing of 339 patients with mucosal melanoma identified four mutually exclusive genomic subtypes: CDK4/MDM2/CCND1, SF3B1-mutated, TP53/ATRX, and mucosal melanoma Triple WT, associated with distinct anatomic sites but similar outcomes. In the tumor microenvironment, we observed reduced T cell infiltration and increased CD163+ tumor-associated macrophages in mucosal melanoma relative to cutaneous melanoma. In matched longitudinal samples, CD163+ tumor-associated macrophages increased with disease progression and immunotherapy resistance. CD163+ tumor-associated macrophages engaged non-regulatory T cells through GAL9-TIM-3 interactions, nominating TIM-3 blockade as a therapeutic strategy for mucosal melanoma. These findings define the distinct aggressive biology of mucosal melanoma and highlight potential therapeutic targets and mechanisms of immune resistance.",
  "abstract_shown": true,
  "affiliations": [
    "Massachusetts General Hospital (MGH) Cancer Center, Boston, MA, USA."
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "name": "Y. Shi"
    },
    {
      "name": "P. Sharma"
    },
    {
      "name": "J.-r. Lin"
    },
    {
      "name": "A. Dedeilia"
    },
    {
      "name": "G. Taratino"
    },
    {
      "name": "R. Pelletier"
    },
    {
      "name": "M. L. Lopez"
    },
    {
      "name": "N. Aygun"
    },
    {
      "name": "M. P. Manos"
    },
    {
      "name": "A. R. Lawless"
    },
    {
      "name": "S. Cohen"
    },
    {
      "name": "Y. D. Lu"
    },
    {
      "name": "M. K. Roelofs"
    },
    {
      "name": "S. M. Pant"
    },
    {
      "name": "J. Chen"
    },
    {
      "name": "D. E. Fisher"
    },
    {
      "name": "R. Beroukhim"
    },
    {
      "name": "C. G. Lian"
    },
    {
      "name": "E. I. Buchbinder"
    },
    {
      "name": "P. K. Sorger"
    },
    {
      "name": "M. Insco"
    },
    {
      "name": "D. Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "G. Boland"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ftj26tc3tf8aw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.02.756347",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756347v1.full",
  "id": "ftj26tc3tf8aw",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756347v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2730|Cutaneous Melanoma Detection and Management"
    ]
  ],
  "openalex": "W7220674515",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756347v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ftj26tc3tf8aw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:14Z",
      "native_id": "10.64898/2026.10.02.756347",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756347v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Genomic classification and immune profiling define mucosal melanoma",
  "title_text": "Genomic classification and immune profiling define mucosal melanoma",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:18Z",
  "url": "https://research.draconitic.com/paper/ftj26tc3tf8aw",
  "venue": "bioRxiv",
  "versions": []
}