Exploiting the type-1 Interferon pathway in the treatment and prediction of breast cancer metastasis — ASN Events
  1. Schedule
  2. Poster Session 2
  3. Exploiting the type-1 Interferon pathway in the treatment and prediction of breast cancer metastasis

Exploiting the type-1 Interferon pathway in the treatment and prediction of breast cancer metastasis (#321)

Jai Rautela 1 2 3 , Nikola Baschuk 1 , Tim Molloy 4 , Sandra O'Toole 4 5 6 , Paul J Hertzog 7 , Robin L Anderson 2 3 , Belinda S Parker 1
  1. La Trobe Institute for Molecular Sciences, La Trobe University, Melbourne, VIC, Australia
  2. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia
  3. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  4. The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia
  5. Sydney Medical School, University of Sydney, Sydney, NSW, Australia
  6. Royal Prince Alfred Hospital, Sydney, NSW, Australia
  7. Monash Institute of Medical Research, Monash University, Melbourne, VIC, Australia

Metastatic disease accounts for almost all breast cancer related deaths. The immune mechanisms that dictate this spread to key sites such as the lung and bone are only now emerging. Our recent work emphasizes the role of the host immune system in restricting breast cancer metastasis, and that the balance between pro- and anti-metastatic immune responses is a critical determinant of metastatic progression. Previous studies in our laboratory using the syngeneic 4T1.2 breast cancer model have shown that breast tumour cells suppress their intrinsic type-1 interferon (IFN) pathway, and hence type-1 IFN secretion, in order to evade host immunosurveillance and metastasise to bone. These findings are supported by a significant correlation between patients with low primary tumour expression of this pathway and increased risk of bone relapse. Taken together, this highlights the type-1 IFN pathway as an attractive target for novel anti-metastatic agents. 

In order to stimulate a systemic IFN response, we have utilized toll-like receptor (TLR) agonists and are currently evaluating their potential as anti-metastatic agents. Treatment of tumour bearing animals with the double-stranded RNA mimetic, Poly(I:C), potently suppressed metastasis to bone and lung and this was associated with enhanced activation of the NK cell compartment. These effects were superior to that observed by direct administration of IFN alpha. In addition to a closer examination of the cellular and molecular mechanisms that underpin the efficacy of these anti-metastatic agents, we are investigating the relevance of combining such therapies with common chemotherapeutics.

Finally, we have uncovered that the expression of a novel set of interferon-regulated genes in a patient’s primary tumour is able to accurately predict metastasis-free survival. Our data suggest that utilisation of these biomarkers and IFN-based therapies may have a significant clinical impact in reducing rates of metastatic breast cancer.

We gratefully acknowledge the support of the Cancer Council of Victoria, Sydney Breast Cancer Foundation and the NHMRC of Australia.