Abstract
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells which accumulate in stress conditions such as infection and tumor. Astaxanthin (ATX) is a well-known antioxidant agent and has a little toxicity. It has been reported that ATX treatment induces antitumor effects via regulation of cell signaling pathways, including nuclear factor erythroid-derived 2-related factor 2 (Nrf2) signaling. In the present study, we hypothesized that treatment with ATX might induce maturation of MDSCs and modulate their immunosuppressive activity. Both in vivo and in vitro treatment with ATX resulted in up-regulation of surface markers such as CD80, MHC class II, and CD11c on both polymorphonuclear (PMN)-MDSCs and mononuclear (Mo)-MDSCs. Expression levels of functional mediators involved in immune suppression were significantly reduced, whereas mRNA levels of Nrf2 target genes were increased in ATX-treated MDSCs. In addition, ATX was found to have antioxidant activity reducing reactive oxygen species level in MDSCs. Finally, ATX-treated MDSCs were immunogenic enough to induce cytotoxic T lymphocyte response and contributed to the inhibition of tumor growth. This demonstrates the role of ATX as a regulator of the immunosuppressive tumor environment through induction of differentiation and functional conversion of MDSCs.
Highlights
Immunotherapy is defined as the treatment of disease by employing the host immune system or immune factors and may complement or substitute for conventional therapies in the treatment of intractable diseases such as cancer [1]
The anti-tumor immune response is decreased by immune suppressors present in the tumor environment, such as myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), tumor-associated macrophages, and type II neutrophils [4]
MDSC expansion can be induced through nuclear factor erythroid-derived 2-related factor 2 (Nrf2)-dependent activation, and Nrf2 pathway contributes to defense mechanisms against oxidative stress exposed to MDSCs [36]
Summary
Immunotherapy is defined as the treatment of disease by employing the host immune system or immune factors and may complement or substitute for conventional therapies in the treatment of intractable diseases such as cancer [1]. The anti-tumor immune response is decreased by immune suppressors present in the tumor environment, such as myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), tumor-associated macrophages, and type II neutrophils [4]. MDSCs account for approximately 2%–3% of cells under normal conditions but are multiplied by several orders of magnitude and accumulate under disease conditions such as cancer [5]. These cells inhibit immune effectors through various mechanisms. MDSCs can directly inhibit the growth and proliferation of T cells by inducing the differentiation of Treg cells through secretion of interleukin (IL)-10 and transforming growth factor-β [5,6] or by breaking down L-arginine, which is Antioxidants 2020, 9, 350; doi:10.3390/antiox9040350 www.mdpi.com/journal/antioxidants
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