{
  "abstract": "Despite the transformative activity of immune checkpoint blockade (ICB) and adoptive cellular therapies in selected malignancies, durable responses remain limited in many solid tumors, in part because tumor-intrinsic and microenvironmental epigenetic programs can restrict immune recognition and antitumor effector function. Enhancer of zeste homolog 2 (EZH2), a catalytic subunit of polycomb repressive complex 2 (PRC2), contributes to this regulation through canonical H3K27 trimethylation-dependent repression, as well as context-dependent functions that extend beyond a simple model of uniform immune suppression. We organize the available evidence into a dual-axis framework in which tumor-intrinsic EZH2/PRC2 activity can regulate major histocompatibility complex class I and II antigen presentation, interferon and viral-mimicry programs, programmed death-ligand 1 (PD-L1), and T helper 1 (TH1)-type chemokines, whereas tumor-extrinsic EZH2 activity influences macrophages, regulatory T cells, CD8 ⁺ T cells, and natural killer (NK) cells. Importantly, these effects are not uniformly immunostimulatory: systemic or prolonged EZH2 perturbation has also been associated with myeloid-derived suppressor cell (MDSC) expansion in selected preclinical settings. Early-phase human studies established the feasibility, but not the incremental clinical benefit, of combining tazemetostat with programmed cell death protein 1 (PD-1)/PD-L1 blockade or chimeric antigen receptor (CAR) T-cell therapy; its subsequent withdrawal after a hematologic safety signal leaves further clinical testing of this strategy to other EZH2- or EZH1/EZH2-directed agents. These observations support mechanism-matched, biomarker-informed, compartment-aware, and temporally controlled EZH2 modulation rather than indiscriminate systemic EZH2 inhibition as the more appropriate framework for future immunotherapy combinations.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatric Surgery, The Second Hospital of Jilin University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yang Bai"
    },
    {
      "affs": [
        0
      ],
      "name": "Huimin Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Ye Gu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a95r8rcbrwpja.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1909464",
  "fulltext_url": null,
  "id": "a95r8rcbrwpja",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1909464/full",
  "language": null,
  "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|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7223692990",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1909464/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/a95r8rcbrwpja.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1909464",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1909464/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "EZH2 at the epigenetic–immune interface: a dual-axis framework for tumor immune evasion and precision combination immunotherapy",
  "title_text": "EZH2 at the epigenetic–immune interface: a dual-axis framework for tumor immune evasion and precision combination immunotherapy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/a95r8rcbrwpja",
  "venue": "Frontiers in Immunology",
  "versions": []
}