Topical Application of Houttuynia cordata Thunb Ethanol Extracts Increases Tumor Infiltrating CD8+/Treg Cells Ratio and Inhibits Cutaneous Squamous Cell Carcinoma in vivo

Houttuynia cordata Thunb (HCT) is a medicinal and edible herb that has beneficial effects on various diseases due to its diuretic, anti-inflammatory, anti-oxidative, anti-microbial, anti-viral, anti-cancer and anti-diabetic proper-ties. Most reports of its anti-cancer activity were conducted in vitro, and its effects on cutaneous squamous cell carcinoma (SCC) have not been investigated yet. Using DMBA/TPA induced SCC mice model, we found that topical treatment by HCT, as well as its bioactive ingredient monomer, efficiently inhibited tumor growth. Mechanistically, tumor infiltrating CD4+, Foxp3+ T regulatory cells (Tregs) were significantly reduced and CD8+/Treg cells ratio was largely increased in tumors after HCT treatment. In addition, several chemokines which function to recruit immune cells were largely reduced in SCC cancer cells treated by HCT in vitro. Our results demonstrate the therapeutic effects of HCT on cutaneous SCC and indicate it might inhibit cancer through regulating tumor infiltrating lymphocytes and the tumor immune microenvironments.