Breast cancer mortality is largely attributed to metastatic spread, with the bone being the most common site of relapse. Consequently, there is a great need for the development of anti-metastatic therapies in order to improve patient survival.
Our recent work highlights the importance of the host immune system during the metastatic process, and suggests that the balance between pro- and anti-metastatic immune responses is critical in dictating the outgrowth of disseminated cells at secondary sites1. Using the immunocompetent 4T1.2 breast tumour model, we have previously shown that tumour cell-derived type-1 interferon (IFN) signaling to the host immune system is critical in restricting metastasis to bone, and that tumour cells suppress an innate type-1 IFN pathway in order to evade these immunosurveillance mechanisms.
Understanding the exact mechanisms by which IFNs protect against bone metastasis may enable the design of therapies able to restrict metastasis to multiple sites. With this in mind, we evaluated the anti-metastatic ability of the double-stranded RNA mimetic, poly(I:C), as a well characterised inducer of IFNs and other mediators involved in anti-viral immune responses. Treatment of the 4T1.2 model with poly(I:C) reduced metastasis to both the bone and lung. Future studies will involve the identification of the immune cell targets and alterations caused by poly(I:C) treatment which are responsible for this anti-metastatic response. With this knowledge, we also aim to combine immunostimulants such as poly(I:C) with commonly used chemotherapeutics to examine combined therapeutic benefits.
Finally, we have demonstrated the clinical relevance of our findings as a transcriptomic analysis of primary breast tumours in a large patient cohort indicated that increased expression of the IFN pathway conferred protection against bone metastasis. We now aim to develop a clinically relevant biomarker that identifies patients likely to develop bone metastases and therefore possibly benefit from IFN-based therapies.