Background: The purpose of this article is to review the current situation with regard to sodium intake in the European Union, provide an update on the efforts being made to reduce the sodium content of food products in various industries via food reformulation and identify the factors motivating food reformulation. Methods: A review was conducted of published literature as well as government and nongovernment organization websites and publications. Results: Food reformulation efforts have been made in the bread, meat, dairy and convenience foods industries. The World Health Organization (WHO) recommendation of b5 g/day of dietary salt intake (b2 g/day sodium) provides an internationally accepted baseline for reformulation efforts. Most Europeans continue to consume salt above the recommended limit. About half of the EU member states have legislated change in the form of taxation, mandatory nutrition labeling and regulated nutrition/health claims. Conclusions: These actions have encouraged sodium reductions in existing food products, but food safety, consumer acceptance, cost and complications arising from the use of sodium alternatives remain limitations to food reformulation.

Targeting immune cells that support tumor growth is an effective therapeutic strategy in tumor entities such as melanoma. M2-like tumor-associated macrophages (TAM) sustain tumor growth by secreting anti-inflammatory cytokines, proteases and growth factors. In this study, we show that a protein derived from M2-like macrophages namely the shedded ectodomain of Lyve-1 (sLyve-1) decreases human HT144 and murine B16F1 melanoma cell proliferation significantly by acting as a decoy receptor for low-molecular weight hyaluronic acid (LMW-HA) although the LMW-HA/Lyve-1 interaction on lymphatic endothelial cells has been described to induce lymphangiogenesis. This is in line with our finding that the number of LYVE-1+ TAM decreases in higher human melanoma stages and that the early growth of B16 transplant tumors is enhanced in Lyve-1 knockout mice when compared to wild-type mice due to an increased melanoma cell proliferation. LYVE-1 expressing TAM are however true M2 macrophages as they co-express typical M2-markers such as CD163 and CD206. The results of the present study highlight the necessity to carefully determine the net effect particular TAM subpopulations have on tumors before establishing a treatment to target these immune cells.

Melanoma is a highly immunogenic tumor with a good response to treatment with immune checkpoint inhibitors. Tumor-associated macrophages (TAMs) play an important immunosuppressive role in such tumors and have therefore been identified as possible future therapeutic targets in oncology. The aim of this study was to identify novel immunoregulatory receptors specifically expressed on TAM. Expression of Slamf9, a member of the signaling lymphocytic-activating molecule (Slam) immunoreceptor family, was found to be upregulated in a gene expression analysis of murine bone marrow-derived macrophages (BMDM) stimulated with tumor-conditioned medium of B16F1 melanoma cells. SLAMF9+ macrophages were identified in human and murine melanomas by using self-generated antibodies against human and murine SLAMF9. A comprehensive immunohistochemical analysis of tissue microarrays detected SLAMF9+ TAM in 73.3% of human melanomas, but also in 95.5% of naevi of melanoma patients and in 50% of naevi from healthy controls. In addition, 20% of melanomas and 2.3% of naevi from melanoma patients displayed a positive SLAMF9 expression also in melanocytic cells. No SLAMF9 expression was detected in naevus cells of healthy donors. Although SLAMF9 has no intracellular signaling motif, a comprehensive functional analysis revealed that the molecule was able to significantly enhance TNF-α secretion after LPS-stimulation. In addition, SLAMF9 delayed the wound closure of RAW 264.7 cells in a scratch assay, while proliferation and cell death were not affected. Taken together, SLAMF9 is a novel type-I-transmembrane receptor with immunomodulatory properties in macrophages. Further studies are required to evaluate whether SLAMF9 classifies as a promising future therapeutic target in melanoma.