{
  "abstract": "Background Colorectal cancer (CRC) progression is shaped by the tumor microenvironment, particularly tumor-associated macrophages (TAMs), which often adopt immunosuppressive functions. CD300e, a myeloid receptor involved in immune regulation, has an uncharacterized role in CRC.Methods Functional studies were conducted in azoxymethane/dextran sodium sulfate and MC38 murine CRC models using CD300e systemic and myeloid-specific CD300e knockout mice, and adoptive transfer experiments assessed macrophage-intrinsic effects. Human studies included analysis of CD300e expression in matched tumor and normal tissue from patients with CRC and in vitro co-culture of patient-derived colon tumor organoids with monocytes to study CD300e induction and TAM polarization.Results In vivo, CD300e deficiency led to reduced tumor burden, enhanced major histocompatibility complex expression on TAMs, and improved T-cell responses. CD300e-deficient macrophages exhibited increased phagocytic activity, antigen presentation, and support for T-cell proliferation and cytotoxicity. Adoptive transfer confirmed that macrophage-intrinsic CD300e expression is sufficient to suppress T-cell function and promote tumor growth. In patients with CRC, CD300e is selectively upregulated in tumor-infiltrating monocytes and macrophages, driving a suppressive phenotype marked by impaired antigen presentation. Tumor-derived signals in vitro induce CD300e expression and promote a protumorigenic macrophage profile.Conclusions Our findings identify CD300e as a critical regulator of macrophage-mediated immune suppression in CRC and a potential target for reprogramming TAMs to enhance immunotherapy.",
  "authors": [
    {
      "affiliations": [
        "Department of Biology, University of Padua, Padua, Italy"
      ],
      "name": "Annica Barizza"
    },
    {
      "affiliations": [
        "Department of Biology, University of Padua, Padua, Italy"
      ],
      "name": "Stefania Vassallo"
    },
    {
      "affiliations": [
        "Department of Biology, University of Padua, Padua, Italy"
      ],
      "name": "Laura Masatti"
    },
    {
      "affiliations": [
        "Molecular Medicine, University of Rome La Sapienza, Rome, Italy"
      ],
      "name": "Mattia Laffranchi"
    },
    {
      "affiliations": [
        "Department of Biology, University of Padua, Padua, Italy"
      ],
      "name": "Sofia Giacometti"
    },
    {
      "affiliations": [
        "Section of Pathology, University of Brescia, Brescia, Italy"
      ],
      "name": "Silvia Lonardi"
    },
    {
      "affiliations": [
        "Section of Pathology, University of Brescia, Brescia, Italy"
      ],
      "name": "Mattia Bugatti"
    },
    {
      "affiliations": [
        "Department of Biology, University of Padua, Padua, Italy"
      ],
      "name": "Sara Coletta"
    },
    {
      "affiliations": [
        "Molecular and Developmental Medicine, University of Siena, Siena, Italy"
      ],
      "name": "Chiara Della Bella"
    },
    {
      "affiliations": [
        "Molecular and Developmental Medicine, University of Siena, Siena, Italy"
      ],
      "name": "Mario Milco D’Elios"
    },
    {
      "affiliations": [
        "Department of Biology, University of Padua, Padua, Italy"
      ],
      "name": "Simone Pizzini"
    },
    {
      "affiliations": [
        "Department of Surgery, Oncology and Gastroenterology, Immunology and Oncology Section, University of Padua, Padova, Italy",
        "Veneto Institute of Oncology IOV – IRCCS, Veneto Oncology Institute, Padua, Italy"
      ],
      "name": "Antonio Rosato"
    },
    {
      "affiliations": [
        "Section of Pathology, University of Brescia, Brescia, Italy"
      ],
      "name": "William Vermi"
    },
    {
      "affiliations": [
        "University of Padua, Padua, Italy"
      ],
      "name": "Matteo Fassan"
    },
    {
      "affiliations": [
        "General Surgery 3, Padua University Hospital, Padua, Italy",
        "Department of Surgery Oncology and Gastroenterology, University of Padua, Padua, Italy"
      ],
      "name": "Gaya Spolverato"
    },
    {
      "affiliations": [
        "Molecular Medicine, University of Rome La Sapienza, Rome, Italy"
      ],
      "name": "Silvano Sozzani"
    },
    {
      "affiliations": [
        "Department of Biology, University of Padua, Padua, Italy"
      ],
      "name": "Enrica Calura"
    },
    {
      "affiliations": [
        "Veneto Institute of Oncology IOV – IRCCS, Veneto Oncology Institute, Padua, Italy",
        "Department of Surgery Oncology and Gastroenterology, University of Padua, Padua, Italy"
      ],
      "name": "Roberta Sommaggio"
    },
    {
      "affiliations": [
        "Department of Biology, University of Padua, Padua, Italy"
      ],
      "name": "Gaia Codolo"
    }
  ],
  "title": "CD300e is a driver of the immunosuppressive tumor microenvironment and colorectal cancer progression via macrophage reprogramming",
  "uid": "189484b1-79f2-5b5e-bf9e-512b79d8be3f"
}