{
  "abstract": "Macrophages are differentiated innate immune cells with niche-responsive plasticity and, in many resident populations, proliferative self-renewal. Single-cell omics, spatial profiling, lineage tracing, and epigenomic studies show that disease-associated macrophages can acquire collagen-producing, lipid-processing, vascular-construction, antigen-presentation, bone-resorptive, or fusion-associated functions. We use lineage-incongruent macrophage state as a descriptive umbrella for phenotypes that deploy a function or regulatory module conventionally associated with another cell type. Six phenomena are compared: functional adaptation, lineage-program borrowing, hybrid identity, intralineage differentiation, cell fusion, and candidate transdifferentiation. We distinguish state plasticity within the myeloid lineage, lineage-ambiguous or hybrid states with co-expression of different lineage programs, and transdifferentiation requiring established cellular origin, source-program attenuation, stable acquisition of a target-lineage network, and target-cell function. Evidence is graded from Level 1 marker observations, through Level 2 single-cell trajectory or spatial support and Level 3 lineage tracing, to Level 4 functional demonstration of the proposed converted identity. Under this framework, TREM2 ⁺ lipid-associated macrophages, osteoclasts, multinucleated giant cells, and most angiogenic macrophages represent specialization, intralineage differentiation, or fusion. TAM-to-CAF transitions are the strongest current candidates for cross-lineage conversion, but the evidence remains model- and organ-dependent, and causal human evidence is limited. A PU.1-anchored rewritable enhancer model provides a testable explanation for how macrophages retain a myeloid scaffold while deploying selected modules. Therapeutic proposals are therefore separated into mechanistic hypotheses, preclinical proof of concept, early clinical evidence, and established myeloid-niche therapies. State-selective targeting is promising, but clinical actionability requires validation of target stability, tissue-specific safety, biomarkers, and efficacy in adequately controlled human studies.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Life Science and Medicine, Department of Colorectal Surgery, The First Affiliated Hospital of USTC (Anhui Provincial Tumor Hospital), University of Science and Technology of China",
    "Department of Immunology, School of Basic Medical Sciences, Anhui Medical University",
    "Department of Rheumatology and Immunology, The Second Affiliated Hospital of Anhui Medical University"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jun Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhiwei Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Shuang Wu"
    },
    {
      "affs": [
        2
      ],
      "name": "Tao Meng"
    },
    {
      "affs": [
        1
      ],
      "name": "Ming Lu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8q83jx8k646bn.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1949327",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735107/",
  "id": "8q83jx8k646bn",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1949327/full",
  "language": "en",
  "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": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2403|Immune cells in cancer"
    ]
  ],
  "openalex": "W7223184954",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1949327/pdf",
  "pmcid": "PMC13735107",
  "pmid": "42990765",
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8q83jx8k646bn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1949327",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1949327/full"
    },
    {
      "first_seen": "2026-11-09T12:20:52Z",
      "native_id": "PMC13735107",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1949327"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
    }
  ],
  "title": "Macrophage plasticity in inflammatory and tumor microenvironments: mechanisms, evidence, and therapeutic opportunities",
  "title_text": "Macrophage plasticity in inflammatory and tumor microenvironments: mechanisms, evidence, and therapeutic opportunities",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:20:52Z",
  "url": "https://research.draconitic.com/paper/8q83jx8k646bn",
  "venue": "Frontiers in Immunology",
  "versions": []
}