Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Immune regulation of breast cancer metastasis (#194)

Clare Y Slaney 1 , Bradley N Bidwell 1 , Jai Rautela 1 , Robin L Anderson 1 , Paul J Hertzog 2 , Belinda S Parker 1
  1. Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Vic, Australia
  2. Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia

Breast cancer is the most common cancer diagnosed in women. The leading cause of death from breast cancer is due to the metastatic spread. Although it has been widely recognized the immune system plays an important role in preventing the establishment of the primary tumor, it remains a question whether the immune system regulates the metastatic process.

In this study, we discovered that tumor cell intrinsic type I interferon pathway stimulates host anti-tumor immune responses and demonstrate the critical function of these anti-tumor immune responses in controlling breast cancer metastasis. In the syngeneic 4T1.2 metastasis model, we utilized mice deficient in adaptive immune system and NK cell function (NOD SCID IL-2 gamma knockout mice) or lacking the Type I IFN signaling pathway (Ifnar1 knockout mice). The ablation of these immune responses greatly reduced the metastasis-free survival rates and enhanced metastasis in mice. In addition, we identified that NK and CD8+ T cells play a key role in the metastatic immunosurvillance. Our data support a breast cancer metastatic immune editing process that provides the fundamental basis for further study of immune surveillance mechanisms that regulate cancer metastasis.