{
  "abstract": "Occasional complete responses (CR) to immune checkpoint inhibitor therapy demonstrate that acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) can be immunosensitive when appropriately targeted. In this study, we analyzed patients with AML/MDS (n = 14) who were treated with the anti-TIM3 sabatolimab and the hypomethylating agent decitabine in a phase Ib clinical trial (NCT03066648) using single-cell RNA and T-cell receptor (TCR) sequencing (n = 6) and functional coculture assays. Unlike T cell–restricted CTLA4 and PD1, TIM3 was broadly expressed across natural killer (NK) cell, myeloid cell, and T-cell populations. Therapy induced the expansion of cytotoxic NK cell subsets and enhanced type I IFN signaling. Fewer than 1% of bone marrow CD8+ T cells displayed a canonical exhaustion phenotype, and treatment preferably expanded small CD8+ T-cell clones in responders. Responders exhibited greater expansion of cytotoxic CD4+ T cells and B cells, as exemplified by a patient with preexisting CD4+ T-cell large granular lymphocyte leukemia (T-LGLL) achieving an outstanding CR lasting 23 months. More than 20% of this patient’s lymphocytes were T-LGLL cells expressing a TCR capable of recognizing autologous blasts. Overall, our results suggest that anti-TIM3 combined with decitabine engages a distinct mechanism of immune activation compared with anti–PD-1 and anti-CTLA4, preferentially expanding NK cell and CD4+ T-cell populations.",
  "abstract_shown": true,
  "affiliations": [
    "Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki, Finland.",
    "Translational Immunology Research Program, Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki, Finland.",
    "iCAN Digital Precision Cancer Medicine Flagship, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.",
    "Department of Computer Science, Aalto University, Espoo, Finland.",
    "Department of Medical and Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.",
    "Centre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria.",
    "Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.",
    "Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.",
    "Department of Clinical Chemistry and Hematology, University of Helsinki, Helsinki, Finland."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jani Huuhtanen",
      "orcid": "0000-0003-2750-4033"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Sofia Forstén",
      "orcid": "0009-0002-4835-3334"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Brittany Ford",
      "orcid": "0000-0003-2301-7799"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Johannes Smolander",
      "orcid": "0000-0003-3872-9668"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Oscar Brück",
      "orcid": "0000-0002-7842-9419"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Sofie Lundgren",
      "orcid": "0000-0003-3146-9816"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Anna Kreutzman",
      "orcid": "0000-0002-5587-8844"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Olli Dufva",
      "orcid": "0000-0002-8084-0282"
    },
    {
      "affs": [
        0,
        1,
        2,
        4
      ],
      "name": "Matti Kankainen",
      "orcid": "0000-0002-4714-9481"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mette Ilander",
      "orcid": "0000-0001-9387-1179"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Hanna Lähteenmäki",
      "orcid": "0000-0001-6773-2677"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Tiina Kasanen",
      "orcid": "0000-0002-5408-1948"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jay Klievink",
      "orcid": "0000-0002-4081-5840"
    },
    {
      "affs": [
        5
      ],
      "name": "Judith Leitner",
      "orcid": "0000-0002-7156-1759"
    },
    {
      "affs": [
        5
      ],
      "name": "Peter Steinberger",
      "orcid": "0000-0001-6848-4097"
    },
    {
      "affs": [
        6
      ],
      "name": "Mika Kontro",
      "orcid": "0000-0001-6353-0664"
    },
    {
      "affs": [
        7
      ],
      "name": "Marc R. Pelletier",
      "orcid": "0000-0003-2860-591X"
    },
    {
      "affs": [
        3
      ],
      "name": "Harri Lähdesmäki",
      "orcid": "0000-0002-0373-139X"
    },
    {
      "affs": [
        7
      ],
      "name": "Catherine Sabatos-Peyton",
      "orcid": "0000-0002-8191-9101"
    },
    {
      "affs": [
        7
      ],
      "name": "Mikael L. Rinne",
      "orcid": "0009-0006-6764-9404"
    },
    {
      "affs": [
        0,
        1,
        2,
        6
      ],
      "name": "Kimmo Porkka",
      "orcid": "0000-0003-4112-5902"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Karita Peltonen",
      "orcid": "0000-0002-3063-451X"
    },
    {
      "affs": [
        0,
        1,
        2,
        8
      ],
      "name": "Satu Mustjoki",
      "orcid": "0000-0002-0816-8241"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2y0cxfd9ftxg1.bib",
  "cited_by": 0,
  "doi": "10.1158/2326-6066.cir-26-0160",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13728807/",
  "id": "2y0cxfd9ftxg1",
  "issns": [
    "2326-6066",
    "2326-6074"
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  "landing_url": "https://doi.org/10.1158/2326-6066.cir-26-0160",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Checkpoint Blockade"
    ],
    [
      "heading",
      "Hematological Cancers"
    ],
    [
      "heading",
      "Immunology"
    ],
    [
      "heading",
      "Immunotherapy"
    ],
    [
      "heading",
      "Leukemias"
    ],
    [
      "heading",
      "Research Articles"
    ],
    [
      "heading",
      "Single Cell Technologies"
    ],
    [
      "heading",
      "Single-cell RNA Sequencing (scRNA-seq)"
    ],
    [
      "heading",
      "Systems Immunology"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7203479193",
  "pdf_url": null,
  "pmcid": "PMC13728807",
  "pmid": "42599272",
  "published": "2026-08-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2y0cxfd9ftxg1.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:21:43Z",
      "native_id": "PMC13728807",
      "source": "pmc",
      "url": "https://doi.org/10.1158/2326-6066.cir-26-0160"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "TIM3 Blockade with Hypomethylating Therapy Restores NK Cell and Cytotoxic CD4+ T-cell Activity in Patients with AML or MDS",
  "title_text": "TIM3 Blockade with Hypomethylating Therapy Restores NK Cell and Cytotoxic CD4+ T-cell Activity in Patients with AML or MDS",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:43Z",
  "url": "https://research.draconitic.com/paper/2y0cxfd9ftxg1",
  "venue": "Cancer Immunology Research",
  "versions": []
}