{
  "abstract": "Introduction: Pancreatic ductal adenocarcinoma (PDAC) responds poorly to immune-checkpoint blockade, and the metabolic organization of its myeloid barrier is incompletely understood.\n\nMethods: We integrated imaging mass cytometry from the phase II trial NCT04177810, three single-cell RNA-seq datasets, two spatial transcriptomic cohorts (12 sections), three survival cohorts, and in vitro siRNA perturbation of MYC, LDHA and SLC16A3 with conditioned-medium assays on THP-1-derived macrophage-like cells and primary human CD8+ T cells.\n\nResults: CD8+ T-cell infiltration increased without objective responses while macrophages remained abundant. Patient-level epithelial MYC and glycolysis programs correlated with SLC16A3 (MCT4) and a macrophage lactate-reception program. Across 12 spatial sections, macrophage-receiver scores were higher around MCT4-high cores (ring 1: 12/12 positive; median difference 0.433; FDR = 0.010), with the strongest state-resolved signal for SPP1/TREM2 macrophages (median difference 0.613; FDR = 0.006); the composition-adjusted effect remained positive (10/12) but was non-significant (FDR = 0.071). Silencing MYC, LDHA or SLC16A3 reduced extracellular lactate and altered conditioned-medium effects, with partial rescue by lactate add-back. Survival associations were cohort-dependent with substantial heterogeneity.\n\nDiscussion: These results define an exploratory, expression-based spatial association between a tumor MYC-LDHA-MCT4 program and an SPP1/TREM2-centered macrophage state, constituting a testable hypothesis rather than evidence of lactate transfer.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Geriatrics, The First Affiliated Hospital of Ningbo University",
    "Department of Emergency Medicine, The First Affiliated Hospital of Ningbo University"
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qianqian Ma"
    },
    {
      "affs": [
        1
      ],
      "name": "Hequn He"
    },
    {
      "affs": [
        0
      ],
      "name": "Ting Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ying Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Chenyang Mao"
    },
    {
      "affs": [
        1
      ],
      "name": "Chao Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Qi Yao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/amr3dyjkkzb80.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1978427",
  "fulltext_url": "https://europepmc.org/articles/PMC13677877",
  "id": "amr3dyjkkzb80",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1978427/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7220408931",
  "pdf_url": "https://europepmc.org/articles/PMC13677877?pdf=render",
  "pmcid": "PMC13677877",
  "pmid": "42898383",
  "published": "2026-10-05",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/amr3dyjkkzb80.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1978427",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1978427/full"
    },
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42898383",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42898383"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "A MYC-LDHA-MCT4 expression program marks an SPP1/TREM2-centered macrophage state in pancreatic ductal adenocarcinoma",
  "title_text": "A MYC-LDHA-MCT4 expression program marks an SPP1/TREM2-centered macrophage state in pancreatic ductal adenocarcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/amr3dyjkkzb80",
  "venue": "Frontiers in Immunology",
  "versions": []
}