{
  "abstract": "Tumor-associated macrophages (TAMs) are pivotal orchestrators of immune evasion, yet the functional significance of the calcineurin signaling pathway in TAM plasticity remains elusive. Analyzing TCGA Lung Cancer datasets and clinical samples, we identified PPP3CA as the major calcineurin catalytic subunit in TAMs, whose downregulation correlates with poor patient survival and tumor progression. Myeloid-specific Ppp3ca knockout in mice accelerated tumor growth, reducing anti-tumor M1-like macrophages and CD8⁺ T cells while enriching pro-tumor M2-like TAMs. In vitro assays confirmed that Ppp3ca deficiency impaired the polarization of TAMs toward the M1 type. Mechanistically, we demonstrated that PPP3CA-mediated regulation of TAM plasticity is dependent on the NF-κB signaling pathway, as Ppp3ca loss significantly blunted NF-κB activation. Furthermore, pharmacological inhibition of calcineurin using cyclosporin A (CsA) effectively recapitulated the myeloid-deficient phenotype, shifting TAMs toward a pro-tumorigenic M2 state and promoting tumor malignancy, providing an experimental explanation for the elevated cancer risk associated with clinical calcineurin inhibitor (CNI) use. Collectively, our findings identify the PPP3CA-NF-κB axis as a pivotal regulator of macrophage plasticity and provide a high-value translational basis for targeting this pathway to remodel the TME in lung cancer immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, China.",
    "East China Normal University-Shanghai Putuo District Central Hospital Collaborative Research Center for Translational Medicine, Shanghai Putuo District Central Hospital, Shanghai 200062, China.",
    "Joint Center for Translational Medicine, Fengxian District Central Hospital, Fengxian District, Shanghai 201499, China.",
    "BRL Medicine, Inc., Shanghai 201109, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ruijie Yang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuxue Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiannan Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruitao Hou"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuqing Chao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yiting Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ning Wang"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Binghe Tan"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Na Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Mingyao Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yongqiang Zhu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Bing Du"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Juliang Qin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d92t8pd6fv57d.bib",
  "cited_by": 0,
  "doi": "10.1016/j.omta.2026.201853",
  "fulltext_url": "https://europepmc.org/articles/PMC13685445",
  "id": "d92t8pd6fv57d",
  "issns": [
    "3117-387X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42909396",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Immune cells in cancer"
    ]
  ],
  "openalex": "W7214755653",
  "pdf_url": "https://europepmc.org/articles/PMC13685445?pdf=render",
  "pmcid": "PMC13685445",
  "pmid": "42909396",
  "published": "2026-09-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d92t8pd6fv57d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42909396",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909396"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
    }
  ],
  "title": "Calcineurin-mediated regulation of macrophage plasticity drives anti-tumor activity.",
  "title_text": "Calcineurin-mediated regulation of macrophage plasticity drives anti-tumor activity.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/d92t8pd6fv57d",
  "venue": "Molecular therapy. Advances",
  "versions": []
}