{
  "abstract": "Background: Anti-tumor immunity relies on coordinated interactions between dendritic cells (DCs) and cytotoxic CD8⁺ T cells to eliminate malignant cells. Mixed lineage kinase domain-like protein (MLKL), a key executioner of necroptosis, has recently been implicated in cancer through necroptosis-independent functions and is being explored as a therapeutic target. However, most studies have focused on tumor cells, whereas the immune-intrinsic functions of MLKL remain poorly understood. In particular, MLKL expression across immune cell subsets and its role in anti-tumor immunity have not been systematically investigated.\n\nResults: Transcriptomic analyses revealed broad MLKL expression across multiple immune cell subsets, including neutrophils, monocytes, dendritic cells, and activated/memory Tcell subsets. Consistent with these findings, MLKL was upregulated in primary mouse immune cells following activation, including Tcell stimulation, bone marrow-derived dendritic cell (BMDC) maturation, and M1 macrophages. Pharmacological inhibition of MLKL impaired BMDC maturation, reduced DC-mediated CD8⁺ T cell priming, and suppressed CD8⁺ T cell activation, proliferation, and cytotoxic killing of B16-OVA tumor cells. Integrated single-cell RNA sequencing analyses from cancer patients receiving immune checkpoint blockade (ICB) further showed that MLKL expression was enriched in activated and effector CD8⁺ T cell subsets. Donor-level analyses showed higher MLKL expression in T cells from ICB responders than in those from non-responders, particularly in post-treatment samples. These findings associate MLKL expression with activated and effector anti-tumor Tcell states and suggest its potential relevance to ICB response.\n\nConclusions: Collectively, these findings show that MLKL is upregulated during immune activation and contributes to DC maturation and CD8⁺ T cell effector responses. Our findings highlight the context-dependent roles of MLKL across tumor and immune compartments and emphasize the importance of considering immune-intrinsic MLKL functions in the development of MLKL-targeted therapies for precision cancer immunotherapy.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13062-026-00931-z.",
  "abstract_shown": true,
  "affiliations": [
    "Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand",
    "Department of Pathology and Krantz Family Center for Cancer Research, Mass General Brigham Cancer Center and Harvard Medical School, Boston, MA USA",
    "Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand",
    "Center of Excellence for Cancer and Inflammation, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nattaya Duangthim"
    },
    {
      "affs": [
        1
      ],
      "name": "Thanpisit Lomphithak"
    },
    {
      "affs": [
        1
      ],
      "name": "Shumeng Hao"
    },
    {
      "affs": [
        1
      ],
      "name": "Francesca S. Gazzaniga"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Siriporn Jitkaew",
      "orcid": "0000-0002-7931-2319"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/96gadjq64gygz.bib",
  "cited_by": 0,
  "doi": "10.1186/s13062-026-00931-z",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732949/",
  "id": "96gadjq64gygz",
  "issns": [
    "1745-6150"
  ],
  "landing_url": "https://doi.org/10.1186/s13062-026-00931-z",
  "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",
      "Research"
    ],
    [
      "openalex",
      "2403|Immunotherapy and Immune Responses"
    ]
  ],
  "openalex": "W7197024832",
  "pdf_url": null,
  "pmcid": "PMC13732949",
  "pmid": "42983857",
  "published": "2026-08-06",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/96gadjq64gygz.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:50Z",
      "native_id": "PMC13732949",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s13062-026-00931-z"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunotherapy and Immune Responses",
      "subfield": "immunology"
    }
  ],
  "title": "Immune-intrinsic MLKL regulates dendritic cell maturation and CD8+ T cell effector function in anti-tumor immunity",
  "title_text": "Immune-intrinsic MLKL regulates dendritic cell maturation and CD8+ T cell effector function in anti-tumor immunity",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:50Z",
  "url": "https://research.draconitic.com/paper/96gadjq64gygz",
  "venue": "Biology Direct",
  "versions": []
}