L-Arginine supplementation inhibits the growth of breast cancer by enhancing innate and adaptive immune responses mediated by suppression of MDSCs in vivoReport as inadecuate




L-Arginine supplementation inhibits the growth of breast cancer by enhancing innate and adaptive immune responses mediated by suppression of MDSCs in vivo - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 16:343

Experimental therapeutics and drug development

Abstract

BackgroundL-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.

MethodsTumor 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-α, and IFN-γ were measured by enzyme-linked immunosorbent assay ELISA and nitric oxide NO levels were measured by the Griess reaction. IFN-γ, T-bet, Granzyme B, ARG-1 and iNOS mRNA levels were examined by real-time RT-PCR.

ResultsL-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-γ, TNF-α, NO levels in splenocytes supernatant, as well as iNOS, IFN-γ, 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.

ConclusionL-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.

KeywordsL-Arginine Breast cancer Tumor immunity MDSCs  Download fulltext PDF



Author: Yu Cao - Yonghui Feng - Yanjun Zhang - Xiaotong Zhu - Feng Jin

Source: https://link.springer.com/







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