{
  "abstract": "Background Tumor-infiltrating lymphocytes (TILs) are established determinants of clinical outcomes in breast cancer. 1–6 While stromal TILs (sTILs) are commonly evaluated due to easier scoring and higher interobserver reproducibility, intraepithelial TILs may provide additional insights into anti-tumor immunity.7 We aimed to comprehensively characterize immunotype-associated cellular landscapes in triple-negative breast cancer (TNBC) and identify features associated with clinical outcomes.Methods 212 TNBC tumors were classified into three immunotypes based on immune infiltrate location and density: immune desert (ID), immune excluded (IE), and immune inflamed (IN). 8 Single-cell spatial transcriptomics was performed on 75 tumors to define the cellular composition and functional states of the tumor microenvironment across immunotypes. Findings were validated and integrated with bulk RNA sequencing data and clinical outcome datasets from FinXX, CALGB-40603, I-SPY 2, and Real-World Clinico-Genomic Data (RWCGD) cohorts.Results Patients with IN tumors had significantly improved outcomes compared with ID tumors. Despite high sTILs, IE tumors showed poor outcomes similar to ID tumors. Single-cell spatial analysis revealed that ID and IE tumors exhibited reduced major histocompatibility complex I/II expression and fewer tumor-resident plasmacytoid dendritic cells (pDCs) compared with IN tumors, which were enriched for interferon-alpha (IFNα) and interferon-gamma (IFNγ) responses. High IFN response scores were associated with favorable outcomes across multiple therapy types in independent datasets. Deconvolution of RWCGD bulk RNA-seq data confirmed that pDC abundance correlated with improved outcomes specifically in hormone receptor–negative subtypes.Conclusions Our study highlights pDCs and IFN signaling as hallmarks of effective anti-tumor immunity in TNBC. Immunotype-based profiling underscores the limited prognostic value of sTILs alone in immune-excluded tumors and supports pDCs and IFN pathways as potential biomarkers for prognosis and therapeutic development in TNBC.",
  "authors": [
    {
      "affiliations": [
        "Department of Quantitative Health Sciences, Mayo Clinic in Florida, Jacksonville, Florida, USA",
        "Department of Pioneering Science, Office of Core Shared Services, Mayo Clinic in Florida, Jacksonville, Florida, USA"
      ],
      "name": "Yi Liu"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Jodi M Carter"
    },
    {
      "affiliations": [
        "Department of Quantitative Health Sciences, Mayo Clinic in Florida, Jacksonville, Florida, USA"
      ],
      "name": "Yaohua Ma"
    },
    {
      "affiliations": [
        "Caris Life Sciences Inc Phoenix, Phoenix, Arizona, USA"
      ],
      "name": "Sachin K Deshmukh"
    },
    {
      "affiliations": [
        "Caris Life Sciences Inc Phoenix, Phoenix, Arizona, USA"
      ],
      "name": "George W Sledge, Jr"
    },
    {
      "affiliations": [
        "Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"
      ],
      "name": "Justin M Balko"
    },
    {
      "affiliations": [
        "Department of Pioneering Science, Office of Core Shared Services, Mayo Clinic in Florida, Jacksonville, Florida, USA"
      ],
      "name": "Jennifer M Kachergus"
    },
    {
      "affiliations": [
        "Department of Pioneering Science, Office of Core Shared Services, Mayo Clinic in Florida, Jacksonville, Florida, USA"
      ],
      "name": "Ji Shi"
    },
    {
      "affiliations": [
        "NanoString Technologies Inc, Seattle, Washington, USA"
      ],
      "name": "Mark Gregory"
    },
    {
      "affiliations": [
        "NanoString Technologies Inc, Seattle, Washington, USA"
      ],
      "name": "Jingjing Gong"
    },
    {
      "affiliations": [
        "Department of Oncology, HUS Helsinki University Hospital, Helsinki, Finland",
        "University of Helsinki, Helsinki, Finland"
      ],
      "name": "Heikki Joensuu"
    },
    {
      "affiliations": [
        "Department of Cancer Biology, Mayo Clinic in Florida, Jacksonville, Florida, USA"
      ],
      "name": "Edith A Perez"
    },
    {
      "affiliations": [
        "The Ohio State University Comprehensive Cancer Center Arthur G James Cancer Hospital and Richard J Solove Research Institute, Columbus, Ohio, USA"
      ],
      "name": "Daniel Stover"
    },
    {
      "affiliations": [
        "UNC School of Medicine, Chapel Hill, North Carolina, USA"
      ],
      "name": "Lisa Carey"
    },
    {
      "affiliations": [
        "Department of Medicine, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA",
        "Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA"
      ],
      "name": "William M Sikov"
    },
    {
      "affiliations": [
        "Department of Oncology, Mayo Clinic Rochester, Rochester, Minnesota, USA"
      ],
      "name": "Roberto Leon-Ferre"
    },
    {
      "affiliations": [
        "Department of Immunology, Mayo Clinic in Florida, Jacksonville, Florida, USA"
      ],
      "name": "Keith L Knutson"
    },
    {
      "affiliations": [
        "Department of Surgery, Mayo Clinic Rochester, Rochester, Minnesota, USA"
      ],
      "name": "Judy C Boughey"
    },
    {
      "affiliations": [
        "Department of Oncology, Mayo Clinic Rochester, Rochester, Minnesota, USA"
      ],
      "name": "James N Ingle"
    },
    {
      "affiliations": [
        "Department of Quantitative Health Sciences, Mayo Clinic Rochester, Rochester, Minnesota, USA"
      ],
      "name": "Krishna R Kalari"
    },
    {
      "affiliations": [
        "Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Rochester, Minnesota, USA"
      ],
      "name": "Fergus J Couch"
    },
    {
      "affiliations": [
        "Department of Quantitative Health Sciences, Mayo Clinic in Florida, Jacksonville, Florida, USA"
      ],
      "name": "Yan W Asmann"
    },
    {
      "affiliations": [
        "Department of Oncology, Mayo Clinic Rochester, Rochester, Minnesota, USA"
      ],
      "name": "Matthew P Goetz"
    },
    {
      "affiliations": [
        "Department of Pioneering Science, Office of Core Shared Services, Mayo Clinic in Florida, Jacksonville, Florida, USA",
        "Department of Cancer Biology, Mayo Clinic in Florida, Jacksonville, Florida, USA"
      ],
      "name": "E Aubrey Thompson"
    },
    {
      "affiliations": [
        "Department of Hematology and Oncology, Mayo Clinic in Florida, Jacksonville, Florida, USA"
      ],
      "name": "Saranya Chumsri"
    }
  ],
  "title": "Spatially resolved single-cell landscape of tumor immunotypes reveals the central role of interferon signaling and plasmacytoid dendritic cells in triple-negative breast cancer",
  "uid": "1d965a1d-8ee6-56bb-a0a2-24733645865d"
}