{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T17:56:48Z","timestamp":1776103008609,"version":"3.50.1"},"reference-count":54,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncol Res Treat"],"abstract":"<jats:p>Introduction: Myeloid-derived suppressor cells (MDSCs) constitute a heterogeneous population that plays a key role in tumor-related immune suppression. MDSCs are immature cells that express the myeloid markers CD11b and Gr1 in mice and accumulate in tumor-bearing mice, including those with HER2\/neu+ breast cancer. We previously reported that tumor regression by anti-neu antibodies requires both innate and adaptive immunity. MDSCs inhibit both types of immunity and are immunosuppressive, particularly for T cells. However, the effect of anti-neu antibodies on MDSCs remains unclear. Methods: HER2+ TUBO tumor-bearing mice were treated with an anti-neu antibody or a control. MDSC populations were analyzed via flow cytometry, and immunosuppressive function was analyzed by a suppression assay. Tumors were analyzed using an RT2-PCR array and RT-PCR for gene expression related to MDSC activation, migration, and function. Additional mice received combination therapy with 5-FU or zoledronic acid to assess enhanced MDSC inhibition and changes in MDSC and tumor-associated macrophage (TAM) populations. Results: The number of MDSCs decreased within 3 days after anti-neu antibody treatment in the tumor and spleen, with the number of tumor MDSCs declining 1 day earlier. The number of monocytic MDSCs was significantly reduced in both tissues (p &gt; 0.05). Anti-neu antibodies also reduced MDSC immunosuppressive activity. Gene expression analysis revealed decreased levels of IL-1\u03b2, VEGF, and CX3CL1, which are linked to MDSC activation and migration. The level of the immunosuppressive factor indoleamine 2,3-dioxygenase was also reduced. Compared with treatment with the antibody alone, combination therapy with 5-FU further suppressed the number of MDSCs and TAMs, resulting in better tumor suppression. Conclusions: Tumor suppression by anti-neu antibodies is associated with a reduction in MDSCs via the inhibition of key MDSC-related factors. MDSCs may be therapeutic targets for increasing Herceptin efficacy in patients with breast cancer.<\/jats:p>","DOI":"10.1159\/000549018","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T16:01:12Z","timestamp":1760716872000},"page":"203-217","source":"Crossref","is-referenced-by-count":1,"title":["Anti-HER2\/Neu Antibody Therapy Inhibits HER2\n                    <sup>+<\/sup>\n                    Breast Cancer by Blocking Myeloid-Derived Suppressor Cell 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