{
  "abstract": "NK cells are critical in anti-tumour immunity through pro-inflammatory cytokine production and direct cytotoxicity. Surgical stress transiently impairs immune function, however its impact on the full spectrum of NK cell cytotoxic pathways has not been systematically examined. Whole blood samples were collected immediately before surgery and within 24 h postoperatively (POD1) from thirty-seven surgical cancer patients from a single tertiary care hospital between August 2021 and March 2026. NK cell interferon gamma (IFNγ) production was measured by flow cytometry in response to various stimuli, including cytokines, NKG2D ligands, LPS, and PMA/Ionomycin. NK cell response was assayed against several tumor target cells, including K562, OVCAR8, SKOV3 and HCT116, each initiating cytotoxicity through imbalances of various receptor interactions. NK cell function was significantly suppressed on POD1, with IFNγ production reduced by 20–50% in response to different activation stimuli and NK cell cytotoxicity significantly reduced by 20–30%, irrespective of the mechanism of tumor cell killing. Specifically, POD1 NK cells exhibited a 30% reduction in killing through activation receptor engagement (K562; p = 0.0143) and missing self (OVCAR8; p = 0 0.006), a 20% reduction in ADCC (SKOV3; p = 0.27 at a 4:1 effector:target ratio), and a 20% reduction in TRAIL-mediated killing (HCT116; p = 0.0009). The latter finding was accompanied by significantly reduced expression of TRAIL on the surface of POD1 NK cells (p = 0.03). These findings suggest surgery leads to a significant and widespread suppression of NK cell effector function that spans multiple activation pathways, reducing clearance of residual cancer cells and highlighting the need to develop strategies to overcome postoperative NK cell dysfunction.\n\nGraphical Abstract:\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00262-026-04438-4.",
  "abstract_shown": true,
  "affiliations": [
    "Cancer Research Program, Ottawa Hospital Research Institute, Ottawa, ON Canada",
    "Department of Biochemistry, Microbiology Immunology, University of Ottawa, Ottawa, ON Canada",
    "Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON Canada",
    "Center for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON Canada"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Marlena Scaffidi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Henna P. Mistry"
    },
    {
      "affs": [
        0
      ],
      "name": "Christiano Tanese de Souza"
    },
    {
      "affs": [
        0
      ],
      "name": "Rafeah Alam"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Rebecca C. Auer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dssyj4bhqwzzw.bib",
  "cited_by": 0,
  "doi": "10.1007/s00262-026-04438-4",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731816/",
  "id": "dssyj4bhqwzzw",
  "issns": [
    "0340-7004",
    "1432-0851"
  ],
  "landing_url": "https://doi.org/10.1007/s00262-026-04438-4",
  "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|Immune Cell Function and Interaction"
    ]
  ],
  "openalex": "W7172440623",
  "pdf_url": null,
  "pmcid": "PMC13731816",
  "pmid": "42975715",
  "published": "2026-08-04",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/dssyj4bhqwzzw.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:56Z",
      "native_id": "PMC13731816",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00262-026-04438-4"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune Cell Function and Interaction",
      "subfield": "immunology"
    }
  ],
  "title": "Surgical stress triggers widespread impairment of NK cell cytotoxicity and cytokine release",
  "title_text": "Surgical stress triggers widespread impairment of NK cell cytotoxicity and cytokine release",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:56Z",
  "url": "https://research.draconitic.com/paper/dssyj4bhqwzzw",
  "venue": "Cancer Immunology, Immunotherapy : CII",
  "versions": []
}