Poster Presentation 29th Lorne Cancer Conference 2017

Describing the immune landscape across metastatic lesions (#107)

Ghamdan Al-Eryani 1 , Simon Junankar 1 , Alex Swarbrick 1
  1. Garvan Institute of Medical Research, Sydney, NSW, Australia

Breast cancer studies over the past decade have increasingly shown the importance of the immune system in malignancy, where high lymphocytic infiltration of the tumour consistently indicates a more favourable prognosis. The significance of the immune system is however best epitomised by the success of recent clinical trials using immune checkpoint inhibitors. Unfortunately, immunotherapy appears to be relatively limited when extended to breast cancer, emphasising how poorly we understand the dynamic cross-talk between cancer cells and the immune system throughout tumour progression and spread. Understanding this relationship is difficult due to several factors. One being the overwhelming diversity of genetically distinct cancer cell populations and immune cells within a tumour and its milieu, which is further amplified as the tumour metastasises. Another being the inherent technical limitations of answering key questions using bulk tumour measurements that ignore the significance of functionally unique populations of immune cell subsets and rare cancer cells that interact in sync to form malignancy. To address some of these limitations, our lab has initiated a project where we will attempt to describe the immune landscape across metastatic lesions obtained from recently deceased breast cancer patients. First at a single-cell level using automated massively parallel single cell RNA sequencing (MARS-Seq). Followed by high dimensional flow cytometry for cell function validation and multiplexed immunofluorescence for spatial depiction. We will also attempt to model some of our key findings using syngeneic mouse models of metastatic breast cancer such as the 4T1 and MMTV-PyMT models. Using the discoveries from this study, we will attempt to develop novel targets for immunotherapy in the hopes of improving the success rate of current breast cancer treatments.