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We hypothesize that Gr1+ myeloid cells transform in phenotype to support tumor cell colonization at the metastatic niche. In the 4T1 model of metastatic breast cancer, we investigate changes in the composition and phenotype of Gr1+ cells between premetastatic disease and early metastasis. Gr1+ cells in the lung were found to transition towards immunosuppressive and tumor\u2010supportive phenotypes with disease progression. While the composition of myeloid cells becomes dysregulated systemically, cells in the blood do not develop tumor\u2010supportive phenotypes, indicating that protumor functions are specific to the lung.\n                    <jats:italic>In vitro<\/jats:italic>\n                    assays demonstrate that Gr1+ cells from early metastatic lungs support tumor cell survival, migration, and proliferation, which is linked to chitinase\u20103\u2010like protein 1 (CHI3L1) signaling. The intravenous injection of polymeric nanoparticles reprograms Gr1+ cell phenotypes, reduces the secretion of CHI3L1, and inhibits metastasis. These findings indicate that dysregulated Gr1+ cells are a therapeutic target for early metastasis and can be targeted with polymeric nanoparticles.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70040","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T01:33:05Z","timestamp":1745458385000},"page":"2860-2881","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Early metastasis is characterized by Gr1+ cell dysregulation and is inhibited by immunomodulatory nanoparticles"],"prefix":"10.1002","volume":"19","author":[{"given":"Jeffrey A.","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia M.","family":"Orbach","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann 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