Poster Presentation 30th Lorne Cancer Conference 2018

Interferons and personalized immunotherapy in breast cancer (#126)

Natasha K Brockwell 1 , Katie Owen 1 , Damien Zanker 1 , Vinod Ganju 2 , Muhammad Alamgeer 3 , Belinda Parker 1
  1. La Trobe Institute for Molecular Science, Bundoora, VICTORIA, Australia
  2. Clinical Translational Research , Hudson Institute for Medical Research, Melbourne , Victoria, Australia
  3. Monash Cancer centre , Melbourne , Victoria, Australia

Immunotherapy has gained momentum as a viable option to treat a subset of cancers. Therapies targeting immune checkpoint proteins such as cytotoxic T‐Lymphocyte antigen 4 (CTLA4) and the programmed death‐1 (PD‐1) receptor have revolutionized the treatment of metastatic melanoma. However, in breast cancer, specifically triple negative breast cancer (TNBC), the application of checkpoint inhibitors targeting the PD-1/PD-L1 axis in TNBC has had underwhelming responses and response is independent of tumour PD-L1 expression. Hence, studies that investigate predictive markers of responders and mechanisms of enhancing response to such immunuotherapies are urgently needed. Using models of TNBC, we demonstrated an interplay between type I interferon (IFN) signaling and tumor cell PD‐L1 expression that impacted therapeutic response. We demonstrated a complete lack of efficacy of anti-PD-1 as a single agent in multiple mouse models of TNBC, however, this lack of efficacy could be overcome with the use of an IFN inducer. The use of an IFN inducer in combination with anti-PD-1 was able to increase intra tumoural lymphocyte numbers and activation as well as induce a specific anti-tumour immune response. This data supported the critical role of immune activation and the tumour microenvironment in immunotherapy response. Our studies have now utilised multiplex immunohistochemistry to characterize the tumour microenvironment in various oncologies before and during conventional therapy to predict those patients likely to respond to immunotherapies such as anti-PD1.   

  1. Brockwell et al., Neoadjuvant Interferons: Critical for Effective PD-1–Based Immunotherapy in TNBC, Cancer Immunol Res, 2017