Post-Surgical Natural Killer T Cell Activation as a Potential Therapy for Metastatic Breast Cancer

Abstract

Natural Killer T (NKT) cells are a specialized group of immune-regulatory T lymphocytes. NKT cells have been shown to limit primary tumor growth and target distant metastatic disease in murine cancer models and in human clinical trials. The focus of this work was to utilize NKT cell activation as a post-surgical immunotherapy in models of metastatic breast cancer. In our model, mammary carcinoma cells were injected into the mammary fat pad of syngeneic mice and primary tumors were resected twelve days later. The following day, mice were treated with NKT cell-activating glycolipids or glycolipid-loaded dendritic cells (DCs) to examine the effect on metastatic disease. Treatment with free glycolipids transiently reduced metastatic disease but did not enhance survival. In contrast, treatment with glycolipid-loaded DCs was effective in limiting metastasis, prolonging survival, and decreasing tumor-associated immune suppression. Our data suggest that NKT cell activation via transfer of glycolipid-loaded self-DCs holds promise as an immunotherapy for metastatic breast cancer.