Increased Chymase-Positive Mast Cells in High-Grade Mucoepidermoid Carcinoma of the Parotid Gland

Abstract

It has long been known that high-grade mucoepidermoid carcinoma (MEC) has a poor prognosis, but the detailed molecular and biological mechanisms underlying this are not fully understood. In the present study, the pattern of chymase-positive mast cells, as well as chymase gene expression, in high-grade MEC was compared to that of low-grade and intermediate-grade MEC by using 44 resected tumor samples of MEC of the parotid gland. Chymase expression, as well as chymase-positive mast cells, was found to be markedly increased in high-grade MEC. Significant increases in PCNA-positive cells and VEGF gene expression, as well as lymphangiogenesis, were also confirmed in high-grade MEC. Chymase substrates, such as the latent transforming growth factor-beta (TGF-β) 1 and pro-matrix metalloproteinase (MMP)-9, were also detected immunohistologically in high-grade MEC. These findings suggested that the increased chymase activity may increase proliferative activity, as well as metastasis in the malignant condition, and the inhibition of chymase may be a strategy to improve the poor prognosis of high-grade MEC of the parotid gland.

Exploring Immunological Effects and Novel Immune Adjuvants in Immunotherapy for Salivary Gland Cancers

“…In a mouse model, lenvatinib with an anti-PD-1 antibody activated CD8+ T cells by reducing TAMs and activating the interferon pathway in multiple types of cancer cell lines [ 121 ]. Although the impact of multi-kinase inhibitors on the TME in SGC has not been determined, VEGF is expressed in MEC and immune-cold AdCCs [ 122 , 123 ] suggesting that multi-kinase inhibitors have the potential to augment the therapeutic efficacy of immunotherapy in SGCs. RT is also considered a candidate for combination therapy with immunotherapies.…”