{
  "abstract": "Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive Epstein–Barr virus (EBV)-associated malignancy with a heterogeneous tumor microenvironment, yet macrophage heterogeneity and tumor-macrophage crosstalk remain poorly defined. Here, we integrate spatial transcriptomic and proteomic profiling with single-cell spatial molecular imaging of ENKTL samples and identify two subgroups defined by distinct macrophage programs. Subgroup 1 is enriched for inflammatory macrophages exhibiting IFN-α/γ responses and immune-regulatory molecules including IDO1 and CD274, whereas Subgroup 2 is immune-quiescent and macrophage-sparse, with its macrophage compartment skewed towards STAB1 macrophages with scavenging features. Notably, an NF-κB-activated and EBV-associated tumor subset is specifically enriched in Subgroup 1, displaying concurrent immunostimulatory and immunoregulatory features that parallel the co-enriched myeloid states and showing reproducible sample-level associations with these myeloid states across datasets. Spatial neighborhood analysis further delineates an inflammation niche where NF-κB tumor cells physically co-localize with these inflammatory macrophages, accompanied by enhanced tumor-myeloid and myeloid-myeloid signaling, implicating a process of tumor-associated myeloid recruitment followed by CCL- and IL1-mediated myeloid self-reinforcement. Critically, higher abundance of this niche correlates with improved survival across independent cohorts, revealing contrasting spatial tumor-immune architectures with prognostic relevance. Together, our study provides a spatially resolved framework for understanding ENKTL biology and guiding immunotherapeutic strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Tsinghua Medicine, Tsinghua University, Beijing, China",
    "Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore",
    "Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China",
    "Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore",
    "Department of Medicine and Surgery, Kore University of Enna, Enna, Italy",
    "Department of Biomedical Informatics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore",
    "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China",
    "Department of Clinical Oncology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China",
    "Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China",
    "Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore",
    "Institute of Advanced Studies Hong Kong, Sun Yat-sen University, Hong Kong SAR, China",
    "Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
    "Department of Pathology, National University Hospital, Singapore, Singapore",
    "Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore",
    "Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore",
    "Department of Haematology-Oncology, National University Cancer Institute Singapore, National University Health System, Singapore, Singapore",
    "Lymphoma Translational Research Laboratory, Division of Cellular and Molecular Research, National Cancer Centre Singapore, Singapore, Singapore",
    "ONCO-ACP, Duke-NUS Medical School, Singapore, Singapore",
    "Center of Excellence for Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania",
    "Director’s Office, National Cancer Centre Singapore, Singapore, Singapore",
    "Office of Education, Duke-NUS Medical School, Singapore, Singapore",
    "Centre for Biomedical Data Science and Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore",
    "Bioinformatics Institute, Agency for Science, Technology and Research, Singapore, Singapore",
    "Immunology Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore",
    "NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore",
    "Advanced Pathology Laboratory, IFOM ETS – The AIRC Institute of Molecular Oncology, Milan, Italy",
    "Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 27,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Lichang Deng",
      "orcid": "0009-0000-2025-9667"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Min Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Reagan Entigu Anak Linton",
      "orcid": "0000-0002-6192-3533"
    },
    {
      "affs": [
        1
      ],
      "name": "Kaijie Hu"
    },
    {
      "affs": [
        3
      ],
      "name": "Shruti Sridhar"
    },
    {
      "affs": [
        4
      ],
      "name": "Giorgio Bertolazzi"
    },
    {
      "affs": [
        1
      ],
      "name": "Sai Mun Leong"
    },
    {
      "affs": [
        1
      ],
      "name": "Ling-Wen Ding"
    },
    {
      "affs": [
        5
      ],
      "name": "Nicholas Syn"
    },
    {
      "affs": [
        1
      ],
      "name": "Shuangyi Fan"
    },
    {
      "affs": [
        1
      ],
      "name": "Cho Mar Myint Wai"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Yi-Qi Li"
    },
    {
      "affs": [
        6,
        7,
        8,
        9,
        10
      ],
      "name": "Jin-Xin Bei",
      "orcid": "0000-0003-1333-407X"
    },
    {
      "affs": [
        11
      ],
      "name": "Jie Xiong",
      "orcid": "0000-0002-7547-5049"
    },
    {
      "affs": [
        11
      ],
      "name": "Wei-Li Zhao"
    },
    {
      "affs": [
        12
      ],
      "name": "Susan Swee-Shan Hue",
      "orcid": "0000-0003-1854-1481"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Joe Poh Sheng Yeong"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Li Yen Chong",
      "orcid": "0000-0002-4623-4633"
    },
    {
      "affs": [
        15
      ],
      "name": "Li-Mei Poon"
    },
    {
      "affs": [
        16,
        17,
        18
      ],
      "name": "Choon Kiat Ong",
      "orcid": "0000-0001-6402-4288"
    },
    {
      "affs": [
        16
      ],
      "name": "Jing Quan Lim"
    },
    {
      "affs": [
        19,
        20
      ],
      "name": "Soon Thye Lim",
      "orcid": "0000-0002-0366-5505"
    },
    {
      "affs": [
        21,
        22,
        23
      ],
      "name": "Jinmiao Chen"
    },
    {
      "affs": [
        22
      ],
      "name": "Hang Xu"
    },
    {
      "affs": [
        3,
        15,
        24
      ],
      "name": "Anand Devaprasath Jeyasekharan",
      "orcid": "0000-0001-9816-6137"
    },
    {
      "affs": [
        25,
        26
      ],
      "name": "Claudio Tripodo"
    },
    {
      "affs": [
        1,
        3,
        24
      ],
      "name": "Siok-Bian Ng",
      "orcid": "0000-0001-6051-6410"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8tbd4tvhn45hk.bib",
  "cited_by": 0,
  "doi": "10.1038/s41375-026-03118-7",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13713596/",
  "id": "8tbd4tvhn45hk",
  "issns": [
    "0887-6924",
    "1476-5551"
  ],
  "landing_url": "https://doi.org/10.1038/s41375-026-03118-7",
  "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",
      "Article"
    ],
    [
      "openalex",
      "2403|Immune cells in cancer"
    ]
  ],
  "openalex": "W7204107852",
  "pdf_url": null,
  "pmcid": "PMC13713596",
  "pmid": "42637876",
  "published": "2026-08-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8tbd4tvhn45hk.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:24:07Z",
      "native_id": "PMC13713596",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41375-026-03118-7"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
    }
  ],
  "title": "Multimodal spatial profiling reveals distinct myeloid-defined ENKTL subgroups and tumor-myeloid cooperativity within prognostic inflammatory niche",
  "title_text": "Multimodal spatial profiling reveals distinct myeloid-defined ENKTL subgroups and tumor-myeloid cooperativity within prognostic inflammatory niche",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:14Z",
  "url": "https://research.draconitic.com/paper/8tbd4tvhn45hk",
  "venue": "Leukemia",
  "versions": []
}