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While toll-like receptor 5 (TLR5) signaling has previously been implicated in promoting myeloid cell recruitment to the ovarian TME, source(s) of ligand and systemic effects on hematopoiesis remain poorly understood. Here, we demonstrate that ovarian cancer disrupts gut barrier integrity, leading to systemic translocation of TLR5 ligands into the peritoneum, blood, and bone marrow. This translocation correlates with enhanced expansion of myeloid progenitors in the bone marrow of wild-type (WT) but not TLR5-deficient (TLR5 KO) mice, leading to enhanced accumulation of monocytes and macrophages into the TME. In the bone marrow, direct TLR5 signaling induced expansion of TLR5-expressing granulocyte-monocyte progenitors, a phenotype recapitulated both using an in vitro colony-forming assay and in a mixed bone marrow chimera model. Acute pharmacologic blockade of TLR5 in tumor-bearing mice altered the composition of tumor-associated myeloid populations, reducing the frequency of monocytes and CCR2-expressing macrophages accumulating within the TME of WT mice. These data reveal that chronic TLR5 signaling, driven by tumor-induced loss of gut barrier integrity, promotes expansion of myeloid cells within the bone marrow and is a host-intrinsic mechanism driving accumulation of immature monocytes and macrophages into the TME.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf172","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T13:34:57Z","timestamp":1764941697000},"source":"Crossref","is-referenced-by-count":0,"title":["Ovarian cancer drives TLR5-dependent expansion of myeloid progenitors through systemic ligand dissemination"],"prefix":"10.1093","volume":"118","author":[{"given":"Sree H","family":"Kolli","sequence":"first","affiliation":[{"name":"Beirne B. Carter Center for Immunology Research, University of Virginia, MR6 Room 3172 A , Charlottesville, VA 22908 ,","place":["United States"]},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, 345 Crispell Drive, PO Box 800734 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell T","family":"McGinty","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, 345 Crispell Drive, PO Box 800734 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3845-2585","authenticated-orcid":false,"given":"Mirna","family":"Perusina Lanfranca","sequence":"additional","affiliation":[{"name":"Beirne B. Carter Center for Immunology Research, University of Virginia, MR6 Room 3172 A , Charlottesville, VA 22908 ,","place":["United States"]},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, 345 Crispell Drive, PO Box 800734 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cara N","family":"Hatzinger","sequence":"additional","affiliation":[{"name":"Beirne B. Carter Center for Immunology Research, University of Virginia, MR6 Room 3172 A , Charlottesville, VA 22908 ,","place":["United States"]},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, 345 Crispell Drive, PO Box 800734 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey M","family":"Putelo","sequence":"additional","affiliation":[{"name":"Beirne B. Carter Center for Immunology Research, University of Virginia, MR6 Room 3172 A , Charlottesville, VA 22908 ,","place":["United States"]},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, 345 Crispell Drive, PO Box 800734 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mika K","family":"Poblete","sequence":"additional","affiliation":[{"name":"Beirne B. Carter Center for Immunology Research, University of Virginia, MR6 Room 3172 A , Charlottesville, VA 22908 ,","place":["United States"]},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, 345 Crispell Drive, PO Box 800734 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Bajgai","sequence":"additional","affiliation":[{"name":"Beirne B. Carter Center for Immunology Research, University of Virginia, MR6 Room 3172 A , Charlottesville, VA 22908 ,","place":["United States"]},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, 345 Crispell Drive, PO Box 800734 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon","family":"Thompson","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, PO Box 800419 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Yu","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, 345 Crispell Drive, PO Box 800734 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francessca N","family":"Azar","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, 345 Crispell Drive, PO Box 800734 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akshita","family":"Mirani","sequence":"additional","affiliation":[{"name":"Beirne B. Carter Center for Immunology Research, University of Virginia, MR6 Room 3172 A , Charlottesville, VA 22908 ,","place":["United States"]},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, 345 Crispell Drive, PO Box 800734 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William A","family":"Petri","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, PO Box 800419 , Charlottesville, VA 22908 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacey L","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Center for Infectious Disease , 6565 Fannin Street, Dunn Tower, 2nd floor, D2-109, Houston, TX 77030 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8604-815X","authenticated-orcid":false,"given":"Melanie R","family":"Rutkowski","sequence":"additional","affiliation":[{"name":"Beirne B. 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