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10.1186/s12885-016-2376-0

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suck abstract from ncbi


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pmid27246354      BMC+Cancer 2016 ; 16 (ä): ä
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  • L-Arginine supplementation inhibits the growth of breast cancer by enhancing innate and adaptive immune responses mediated by suppression of MDSCs in vivo #MMPMID27246354
  • Cao Y; Feng Y; Zhang Y; Zhu X; Jin F
  • BMC Cancer 2016[]; 16 (ä): ä PMID27246354show ga
  • Background: L-Arg is involved in many biological activities, including the activation of T cells. In breast cancer patients, L-Arg is depleted by nitric oxide synthase 2 (NOS2) and arginase 1 (ARG-1) produced by myeloid-derived suppressor cells (MDSCs). Our aim was to test whether L-Arg supplementation could enhance antitumor immune response and improve survivorship in a rodent model of mammary tumor. Methods: Tumor volumes in control and L-Arg treated 4 T1 tumor bearing (TB) BALB/c mice were measured and survival rates were recorded. The percentages of MDSCs, dendritic cells (DCs), regulatory T cells (Tregs), macrophages, CD4+ T cells, and CD8+ T cells were examined by flow cytometry. Additionally, levels of IL-10, TNF-?, and IFN-? were measured by enzyme-linked immunosorbent assay (ELISA) and nitric oxide (NO) levels were measured by the Griess reaction. IFN-?, T-bet, Granzyme B, ARG-1 and iNOS mRNA levels were examined by real-time RT-PCR. Results: L-Arg treatment inhibited tumor growth and prolonged the survival time of 4 T1 TB mice. The frequency of MDSCs was significantly suppressed in L-Arg treated TB mice. In contrast, the numbers and function of macrophages, CD4+ T cells, and CD8+ T cells were significantly enhanced. The IFN-?, TNF-?, NO levels in splenocytes supernatant, as well as iNOS, IFN-?, Granzyme B mRNA levels in splenocytes and tumor blocks were significantly increased. The ARG-1 mRNA level in tumor blocks, the frequency of Tregs, and IL-10 level were not affected. Conclusion: L-Arg supplementation significantly inhibited tumor growth and prolonged the survival time of 4 T1 TB mice, which was associated with the reduction of MDSCs, and enhanced innate and adaptive immune responses.
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