{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:11:23Z","timestamp":1791655883903,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center","award":["2023KYQD002"],"award-info":[{"award-number":["2023KYQD002"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32400758"],"award-info":[{"award-number":["32400758"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470974"],"award-info":[{"award-number":["32470974"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472960"],"award-info":[{"award-number":["82472960"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>N-acetylcysteine (NAC) is a widely used antioxidant. It has also attracted significant research interest with regard to its role in cancer progression, although the mechanisms involved remain controversial and poorly understood. Here, using murine models of breast cancer metastasis, we found that systemic NAC administration significantly enhanced pulmonary metastasis without altering primary tumor growth in immunocompetent mice, whereas this metastasis-promoting property of NAC was abrogated in T cell-deficient mice. This phenomenon was not due to the direct effects of NAC on T cells or tumor cells, since in vitro studies indicated that NAC exhibited no impact on the effector functions of T cells or the malignant behavior of breast cancer cells. Mechanistically, we demonstrated that NAC endows neutrophils with an immunosuppressive phenotype, which is characterized by the upregulation of immunosuppressive genes, and these NAC-educated neutrophils potently suppress the activation and effector functions of T cells. Collectively, our study reveals a previously unrecognized role played by NAC in regulating breast cancer lung metastasis by orchestrating the myeloid-dependent suppression of anti-tumor T cell immunity and suggests a need to consider immune-mediated mechanisms when evaluating the systemic impact of antioxidant agents in cancer patients.<\/jats:p>","DOI":"10.3390\/ijms27010526","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T13:35:47Z","timestamp":1767620147000},"page":"526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antioxidant N-Acetylcysteine Facilitates Breast Cancer Metas-Tasis via Immunosuppressive Reprogramming of Neutrophils"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9240-8807","authenticated-orcid":false,"given":"Jiawen","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei 230032, China"},{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601, China"},{"name":"Joint Research Center for Food Derived Functional Factors and Synthetic Biology of IHM, School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huige","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei 230032, China"},{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601, China"},{"name":"Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghao","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601, China"},{"name":"Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9789-0596","authenticated-orcid":false,"given":"Zheng","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei 230032, China"},{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601, China"},{"name":"State Key Laboratory of Immune Response and Immunotherapy, Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41580-023-00645-4","article-title":"Understanding mechanisms of antioxidant action in health and disease","volume":"25","author":"Halliwell","year":"2024","journal-title":"Nat. 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