Poster Presentation Eradicate Cancer 2018

Working towards personalized immunotherapy in breast cancer (#103)

Natasha Brockwell 1 , J Rautela 2 , M Alamger 3 , V Ganju 4 , B. S. Parker 1
  1. La Trobe Institute for Molecular Science, Bundoora, VICTORIA, Australia
  2. Walter and Eliza Hall institute , Melbourne, VIC, Australia
  3. Monash Cancer centre , Melbourne , Victoria, Australia
  4. Clinical Translational Research , Hudson Institute for Medical Research, Melbourne , Victoria, Australia

Immunotherapy has revolutionized cancer treatment, with sustained responses to immune checkpoint inhibitors reported in a number of malignancies. Such therapeutics are now being trialed in aggressive or advanced cancers that are heavily reliant on untargeted therapies, such as triple negative breast cancer. However, responses have been underwhelming to date and are very difficult to predict, leading to an inability to accurately weigh up the benefit-to-risk ratio for their implementation. The tumor immune microenvironment has been closely linked to immunotherapeutic response, with superior responses observed in patients with T cell-inflamed or ‘hot’ tumors. Therefore, there is a need to characterize tumour infiltrating lymphocytes (TILs) in patients to give us a deeper understanding of tumour behaviour and expected response to therapy. Utilizing multiplexed immunohistochemistry on tissues from breast cancer patients pre, mid and post chemotherapy we have demonstrated the superior prognostic information that can be gathered from TIL characterisation. Our findings demonstrate that analysis of immune cell types and their activation status can be used to predict response to chemotherapy. Furthermore, we have demonstrated the benefit of sequential biopsies throughout neoadjuvant chemotherapy administration, where specific cell populations at mid and post chemo can predict patient survival. Similar characterization techniques have now been applied for pre-treatment mesothelioma tissues, where baseline immune status can predict response to therapy, and most importantly, response to immunotherapy. These studies offer rationale for pre- and post-tumour biopsies to monitor benefit and response to immunotherapeutics.