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These immunological changes correlated with reduced tumor growth and prolonged survival. Mice in the MSC1d group exhibited elevated serum levels of pro-inflammatory and anti-tumor cytokines (TNF-\u03b1, IFN-\u03b3, IL-6, and IL-17), alongside decreased concentrations of immunosuppressive cytokines (TGF-\u03b2 and IL-10). Tumor tissue analysis revealed increased infiltration of NK cells expressing markers associated with antitumor activity (IFN-\u03b3-producing CD178\u207a), CD80\u207a\/CD86\u207a\/I-A\u207a TNF-\u03b1-producing DCs, Th1-type CD4\u207a T cells, and Granzyme B-expressing CD8\u207a cytotoxic T lymphocytes (CTLs). Additionally, spleens of MSC1d-treated mice displayed significantly elevated populations of CD11c\u207a DCs, TNF-\u03b1\/IFN-\u03b3-secreting NK cells, CD4\u207a Th1 and Th17 cells, and CD8\u207a CTLs expressing markers associated with cytotoxic function (TNF-\u03b1, IFN-\u03b3, and IL-17). Conversely, late MSCs administration (MSC14d) was associated with immunosuppression. Tumors from MSC14d-treated mice showed a decreased presence of IFN-\u03b3\u207a and IL-17\u207a NK1.1\u207a cells, F4\/80\u207a macrophages, IL-12\u207a DCs, and cytotoxic T cells. Spleens from these mice revealed a significant expansion of regulatory T cell (Treg)-like populations, including CD25\u207b, FoxP3\u207b, CD25\u207aFoxP3\u207b cells, and TGF-\u03b2\/IL-10-producing CD3\u207a and CD4\u207a T cells. Furthermore, serum levels of immunosuppressive mediators TGF-\u03b2 and vascular endothelial growth factor (VEGF) were significantly elevated in the MSC14d group. Collectively, these findings demonstrate that the immunomodulatory effects of MSCs on breast cancer are highly dependent on the timing of their administration. Mesenchymal stem cells delivered during early tumor development enhance phenotypes consistent with antitumor potential and suppress tumor progression, whereas administration during later stages promotes immune evasion and tumor growth.<\/jats:p>","DOI":"10.1177\/09636897251414744","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T09:02:24Z","timestamp":1769590944000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Temporal dynamics of mesenchymal stem cell administration influence immune modulation in a 4T1 breast cancer model"],"prefix":"10.1177","volume":"35","author":[{"given":"Dragana","family":"Papic","sequence":"first","affiliation":[{"name":"Department of Genetics, Center for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7474-7495","authenticated-orcid":false,"given":"Dragica","family":"Pavlovic","sequence":"additional","affiliation":[{"name":"Department of Genetics, Center for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danijela","family":"Niciforovic","sequence":"additional","affiliation":[{"name":"Center for Internal Oncology, University Clinical Center Kragujevac, Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6525-128X","authenticated-orcid":false,"given":"Vladimir","family":"Jurisic","sequence":"additional","affiliation":[{"name":"Patophysiology Department, Faculty of Medical Science, University of Kragujevac, Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5948-9902","authenticated-orcid":false,"given":"Vladislav","family":"Volarevic","sequence":"additional","affiliation":[{"name":"Department of Genetics, Center for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia"},{"name":"Department of Microbiology and Immunology Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16071255"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2025.1639439"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-022-00952-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-025-00688-7"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.05.015"},{"issue":"8","key":"e_1_3_3_8_2","article-title":"The role of mesenchymal stem cell-derived exosomes in tumor progression","volume":"47","author":"Harrel CR","year":"2023","unstructured":"Harrel CR, Djonov V, Volarevic A, Pavlovic D, Volarevic V. 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