{"entity": "researcher", "timestamp": "2026-08-25T12:56:51.912Z", "family": "Sarhan", "given": "Dhifaf", "initials": "D", "orcid": "0000-0003-0196-4496", "affiliations": ["Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/21138e97f7094430a43dfb5d24f3d5f8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/21138e97f7094430a43dfb5d24f3d5f8"}}, "publications": [{"entity": "publication", "iuid": "41cc9eb753954a26aec65b8fe6b92cbb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/41cc9eb753954a26aec65b8fe6b92cbb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/41cc9eb753954a26aec65b8fe6b92cbb"}}, "title": "FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation.", "authors": [{"family": "Gultekin", "given": "Okan", "initials": "O"}, {"family": "Gonzalez-Molina", "given": "Jordi", "initials": "J"}, {"family": "Hardell", "given": "Elin", "initials": "E"}, {"family": "Moyano-Galceran", "given": "Lidia", "initials": "L", "orcid": "0000-0001-9219-6394", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/84dfd710b5884f46a17ec259e18546b0.json"}}, {"family": "Mitsios", "given": "Nicholas", "initials": "N", "orcid": "0000-0001-6243-4953", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9443771d4c464bf6b18fc130b329444b.json"}}, {"family": "Mulder", "given": "Jan", "initials": "J", "orcid": "0000-0003-3717-5018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/40ed8170792444b491519e499d51c434.json"}}, {"family": "Kokaraki", "given": "Georgia", "initials": "G", "orcid": "0000-0002-6372-4239", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ff66c2a88e6744a19913891579e5b4ae.json"}}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Sarhan", "given": "Dhifaf", "initials": "D", "orcid": "0000-0003-0196-4496", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21138e97f7094430a43dfb5d24f3d5f8.json"}}, {"family": "Lehti", "given": "Kaisa", "initials": "K", "orcid": "0000-0001-9110-8719", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/613d944b4c8c4942b871ba87f580e53e.json"}}, {"family": "Carlson", "given": "Joseph W", "initials": "JW"}], "type": "journal article", "published": "2021-11-19", "journal": {"title": "NPJ Precis Oncol", "issn": "2397-768X", "volume": "5", "issue": "1", "pages": "97", "issn-l": null}, "abstract": "Uterine sarcomas are rare but deadly malignancies without effective treatment. Immunotherapy is a promising new approach to treat these tumors but has shown heterogeneous effects in sarcoma patients. With the goal of identifying key factors for improved patient treatment, we characterized the tumor immune landscape in 58 uterine sarcoma cases with full clinicopathological annotation. Immune cell characterization revealed the overall prevalence of FOXP3+ cells and pro-tumor M2-like macrophages. Hierarchical clustering of patients showed four tumor type-independent immune signatures, where infiltration of FOXP3+ cells and M1-like macrophages associated with favorable prognosis. High CD8+/FOXP3+ ratio in UUS and ESS correlated with poor survival, upregulation of immunosuppressive markers, extracellular matrix (ECM)-related genes and proteins, and YAP activation. This study shows that uterine sarcomas present distinct immune signatures with prognostic value, independent of tumor type, and suggests that targeting the ECM could be beneficial for future treatments.", "doi": "10.1038/s41698-021-00236-6", "pmid": "34799669", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8604926"}, {"db": "pii", "key": "10.1038/s41698-021-00236-6"}], "notes": [], "created": "2026-08-21T11:54:22.810Z", "modified": "2026-08-21T11:54:22.968Z"}, {"entity": "publication", "iuid": "27718d5dd8274d77ba85771296bea337", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/27718d5dd8274d77ba85771296bea337.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/27718d5dd8274d77ba85771296bea337"}}, "title": "Targeting MARCO and IL37R on Immunosuppressive Macrophages in Lung Cancer Blocks Regulatory T Cells and Supports Cytotoxic Lymphocyte Function.", "authors": [{"family": "La Fleur", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "He", "given": "Fei", "initials": "F"}, {"family": "Pelicano", "given": "Catarina", "initials": "C", "orcid": "0000-0002-7039-2922", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f7387f29e422468fa2241e139ffab7e3.json"}}, {"family": "Zhou", "given": "Chikai", "initials": "C", "orcid": "0000-0001-9653-3466", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/95fabbd5aade45bab5773d83772dfcfc.json"}}, {"family": "He", "given": "Chenfei", "initials": "C"}, {"family": "Palano", "given": "Giorgia", "initials": "G", "orcid": "0000-0002-7572-7699", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/67dbbabff01c45af81855c6abb28e6bc.json"}}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A", "orcid": "0000-0002-4394-2634", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/227a0142881848f4a1635d66cf52e673.json"}}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b4b9d0f748440e19db93d4543bbe25f.json"}}, {"family": "Ravetch", "given": "Jeffrey V", "initials": "JV"}, {"family": "Karlsson", "given": "Mikael C I", "initials": "MCI"}, {"family": "Sarhan", "given": "Dhifaf", "initials": "D", "orcid": "0000-0003-0196-4496", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21138e97f7094430a43dfb5d24f3d5f8.json"}}], "type": "journal article", "published": "2021-02-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "81", "issue": "4", "pages": "956-967", "issn-l": "0008-5472"}, "abstract": "The progression and metastatic capacity of solid tumors are strongly influenced by immune cells in the tumor microenvironment. In non-small cell lung cancer (NSCLC), accumulation of anti-inflammatory tumor-associated macrophages (TAM) is associated with worse clinical outcome and resistance to therapy. Here we investigated the immune landscape of NSCLC in the presence of protumoral TAMs expressing the macrophage receptor with collagenous structure (MARCO). MARCO-expressing TAM numbers correlated with increased occurrence of regulatory T cells and effector T cells and decreased natural killer (NK) cells in these tumors. Furthermore, transcriptomic data from the tumors uncovered a correlation between MARCO expression and the anti-inflammatory cytokine IL37. In vitro studies subsequently showed that lung cancer cells polarized macrophages to express MARCO and gain an immune-suppressive phenotype through the release of IL37. MARCO-expressing TAMs blocked cytotoxic T-cell and NK-cell activation, inhibiting their proliferation, cytokine production, and tumor killing capacity. Mechanistically, MARCO+ macrophages enhanced regulatory T (Treg) cell proliferation and IL10 production and diminished CD8 T-cell activities. Targeting MARCO or IL37 receptor (IL37R) by antibody or CRISPR knockout of IL37 in lung cancer cell lines repolarized TAMs, resulting in recovered cytolytic activity and antitumoral capacity of NK cells and T cells and downmodulated Treg cell activities. In summary, our data demonstrate a novel immune therapeutic approach targeting human TAMs immune suppression of NK- and T-cell antitumor activities. SIGNIFICANCE: This study defines tumor-derived IL37 and the macrophage scavenger receptor MARCO as potential therapeutic targets to remodel the immune-suppressive microenvironment in patients with lung cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/4/956/F1.large.jpg.", "doi": "10.1158/0008-5472.CAN-20-1885", "pmid": "33293426", "labels": [], "xrefs": [{"db": "pii", "key": "0008-5472.CAN-20-1885"}], "notes": [], "created": "2026-08-21T12:28:52.228Z", "modified": "2026-08-21T12:28:52.468Z"}]}