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Bacterial lipopolysaccharides (LPS) have been widely demonstrated in various types of solid tumors. LPS can promote the malignant progression of tumors, which mechanism has not yet been fully elucidated. In this study, a type of MDSC\u2010like tumor cells (MLTCs) is found in tumor tissues induced by low\u2010dose and long\u2010term LPS stimulation. MLTCs can simultaneously express tumor cell and MDSCs markers. Similar to MDSCs, MLTCs can produce arginine, nitric oxide, and reactive oxygen species and inhibit the activity of NK and T cells to promote the formation of an immunosuppressive microenvironment. MLTCs can also promote tumor cell proliferation and vasculogenic mimicry formation. CRISPR\u2010Cas9 activity screening studies identified RNA\u2010binding Fox\u20101 homolog 3 (Rbfox3) as a critical protein for MLTCs formation after LPS treatment. Rbfox3 can transcriptionally regulate the expression of Ass1 in the form of phase\u2010separated particles. Crocin can inhibit the generation of MLTCs by disrupting phase\u2010separated particles of Rbfox3 and enhance the anti\u2010tumor effects of immune checkpoint inhibitors (ICIs).<\/jats:p>","DOI":"10.1002\/advs.202404585","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T09:14:05Z","timestamp":1736241245000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Rbfox3 Promotes Transformation of MDSC\u2010Like Tumor Cells to Shape Immunosuppressive Microenvironment"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhiyang","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai University Tianjin 300450 China"},{"name":"Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs Tianjin International Joint Academy of Biomedicine Tianjin 300457 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