{
  "abstract": "Purpose: Regulatory T cells (Tregs) promote tumor escape. Here we show CD45RA−FoxP3highCD4+ activated Tregs (aTreg, Fr. II) acquired a Th17-like phenotype in acute myeloid leukemia (AML). The primary objective of this study was to explore the specific roles of non-classical monocytes in regulating the increased Fr. II plasticity to Th17-like phenotype to form the immunosuppressive microenvironment.\n\nMethods: We stratified phenotypically heterogeneous FoxP3⁺CD4⁺ T cells from AML patients into three subsets based on FoxP3 and CD45RA, aiming to dissect their functional diversity by flow cytometry. Flow cytometric sorting, co-culture assays, in vitro neutralization experiments, and JAK2 blockade assays were employed to demonstrate that non-classical monocytes induce Th17-like Fr. II cells through the IL-6/JAK2/STAT3 pathway.\n\nResults: CD45RA−FoxP3high Fr. II, which performed a major inhibitory role in three FoxP3⁺CD4⁺ T subsets, were reduced in numbers but enhanced their immunosuppressive capacity in AML. Besides, Fr. II had a Th17-like phenotypic shift (marked by augmented IL-17 A and RORγt expression). Co-culture assays and in vitro neutralization experiments demonstrated that IL-6 secreted by non-classical monocytes regulates the conversion of Fr. II toward a Th17-like phenotype. Furthermore, JAK2 inhibitor reduced the phosphorylation of STAT3 and impaired Th17-like differentiation potency of Fr. II in AML patients. Notably, IL-17 A⁺ Fr. II were reduced after treatment.\n\nConclusions: Taken together, we found that non-classical monocytes drive the differentiation of Th17-like Fr. II via the IL-6/JAK2/STAT3 signaling pathway in AML. IL-17 A⁺ Fr. II may correlate with disease activity. Our finding reveals a new immune-evasion mechanism in AML, and offers a potential therapeutic target in the immunotherapy of AML.\n\nGraphical Abstract: IL-6/JAK2/STAT3 axis mediates non-classical monocyte-induced Th17-like conversion of activated Tregs in acute myeloid leukemia patients. This study demonstrates that CD14-CD16+ nonclassical monocytes secrete IL-6, which binds to IL-6R on aTregs. This triggers downstream JAK2 phosphorylation, followed by STAT3 phosphorylation and subsequent RORγt expression, thereby stimulating aTregs to secrete IL-17 and further aggravating the severity of AML.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16619-6.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, #218 Jixi Road, Hefei, Anhui, 230032, China.",
    "Clinical Medical College of Anhui Medical University, Hefei, Anhui, China.",
    "Department of Blood Transfusion, The Third People's Hospital of Datong, Datong, Shanxi, China.",
    "Anhui Medical University, Hefei, Anhui, China.",
    "Department of Hematology, The First Affiliated Hospital of Anhui Medical University, #218 Jixi Road, Hefei, Anhui, 230032, China.",
    "Department of Hematology, The First Affiliated Hospital of Anhui Medical University, #218 Jixi Road, Hefei, Anhui, 230032, China. huangjianyao@sohu.com.",
    "Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, #218 Jixi Road, Hefei, Anhui, 230032, China. zonglu@fy.ahmu.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiaoran Dai"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Yuanling Zheng"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Xu Liu"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Ruoyu Huang"
    },
    {
      "affs": [
        4
      ],
      "name": "Mei Fu"
    },
    {
      "affs": [
        0
      ],
      "name": "Meijuan Zheng",
      "orcid": "0000-0002-7378-3355"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuanhong Xu",
      "orcid": "0000-0002-1637-3800"
    },
    {
      "affs": [
        5
      ],
      "name": "Jianyao Huang"
    },
    {
      "affs": [
        6
      ],
      "name": "Lu Zong",
      "orcid": "0000-0002-7219-5076"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7rn3dceze2teh.bib",
  "cited_by": 0,
  "doi": "10.1186/s12885-026-16619-6",
  "fulltext_url": "https://europepmc.org/articles/PMC13721268",
  "id": "7rn3dceze2teh",
  "issns": [
    "1471-2407"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958106",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7171371287",
  "pdf_url": "https://europepmc.org/articles/PMC13721268?pdf=render",
  "pmcid": "PMC13721268",
  "pmid": "42958106",
  "published": "2026-07-28",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/7rn3dceze2teh.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:48Z",
      "native_id": "MED:42958106",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958106"
    },
    {
      "first_seen": "2026-11-03T12:21:59Z",
      "native_id": "PMC13721268",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12885-026-16619-6"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "IL-6/JAK2/STAT3 axis mediates non-classical monocyte-induced Th17-like conversion of activated Tregs in acute myeloid leukemia patients.",
  "title_text": "IL-6/JAK2/STAT3 axis mediates non-classical monocyte-induced Th17-like conversion of activated Tregs in acute myeloid leukemia patients.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:59Z",
  "url": "https://research.draconitic.com/paper/7rn3dceze2teh",
  "venue": "BMC cancer",
  "versions": []
}