Decreased NK cell cytotoxicity and increased T regulatory cells facilitate progression of metastatic murine melanoma

Abstract

Malignant melanoma is the most aggressive form of skin cancer. Metastatic dissemination in distant organs is one of the hallmarks of melanoma progression. Immunosuppression and tumour escape from immune surveillance are thought to be the major factors responsible for the establishment and progression of melanoma; however, the exact mechanisms leading to decreased anti-tumour immunity are not completely understood. We aimed to analyse the anti-tumour immune response during hematogenous metastasis using a B16-F1 metastatic melanoma model in C57BL/6 mice. At 21 days after tumour cell inoculation, rapid metastatic melanoma growth was observed, reflected through the increased incidence, number and size of metastatic colonies in the lungs (B16-F1). Phenotypic analyses of splenocytes revealed an increased percentage of CD3 +T cells, a markedly reduced percentage of CD19 +B cells and an increased percentage and absolute number of CD4 +Foxp3 +T regulatory cells. The cytotoxic activities of total splenocytes and isolated NK cells were significantly decreased in tumour-bearing mice. Thus, the metastatic progression of melanoma in this model is associated with diminished NK cytotoxicity, which may be due to an increased expansion of suppressive CD4 +Foxp3 sup+T regulatory cells in the spleen.