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However, research on the phenotypic and functional heterogeneity of MDSCs in tumor-bearing hosts and across different disease stage is limited. Here we subdivide M-MDSCs based on CD115 expression and report that CD115<jats:sup>\u2212<\/jats:sup> M-MDSCs are functionally distinct from CD115<jats:sup>+<\/jats:sup> M-MDSCs. CD115<jats:sup>\u2212<\/jats:sup> M-MDSCs increased in bone marrow and blood as tumors progressed. Transcriptome analysis revealed that CD115<jats:sup>\u2212<\/jats:sup> M-MDSCs expressed higher levels of neutrophil-related genes. Moreover, isolated CD115<jats:sup>\u2212<\/jats:sup> M-MDSCs had higher potential to be differentiated into PMN-MDSCs compared with CD115<jats:sup>+<\/jats:sup> M-MDSCs. Of note, CD115<jats:sup>\u2212<\/jats:sup> M-MDSCs were able to differentiate into both olfactomedin 4 (OLFM4)<jats:sup>hi<\/jats:sup> and OLFM4<jats:sup>lo<\/jats:sup> PMN-MDSCs, whereas CD115<jats:sup>+<\/jats:sup> M-MDSCs differentiated into a smaller proportion of OLFM4<jats:sup>lo<\/jats:sup> PMN-MDSCs. In vivo, M-MDSC to PMN-MDSC differentiation occurred most frequently in bone marrow while M-MDSCs preferentially differentiated into tumor-associated macrophages in the tumor mass. Our study reveals the presence of previously unrecognized subtypes of CD115<jats:sup>\u2212<\/jats:sup> M-MDSCs in tumor-bearing hosts and demonstrates their cellular plasticity during tumorigenesis.<\/jats:p>","DOI":"10.1038\/s42003-023-04650-3","type":"journal-article","created":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T19:53:55Z","timestamp":1679860435000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["CD115\u2212 monocytic myeloid-derived suppressor cells are precursors of OLFM4high polymorphonuclear myeloid-derived suppressor cells"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-2330","authenticated-orcid":false,"given":"Yunyun","family":"Zou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuhiko","family":"Kamada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3671-1029","authenticated-orcid":false,"given":"Seung-Yong","family":"Seong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6633-1932","authenticated-orcid":false,"given":"Sang-Uk","family":"Seo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"4650_CR1","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nrc1586","volume":"5","author":"W Zou","year":"2005","unstructured":"Zou, W. 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