E-Poster Presentation 34th Lorne Cancer Conference 2022

Immune Regulation Of The Premetastatic Niche Formation In Triple-negative Breast Cancer (#338)

Laura Rodriguez de la Fuente 1 2 3 , Yolanda Colino Sanguino 2 4 , Jeron Venhuizen 1 , Andrew MK. Law 1 3 , Fatima Valdes-Mora 2 4 , David Gallego-Ortega 1 3 5
  1. Tumour Development Laboratory, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia
  2. Cancer Epigenetic Biology and Therapeutics, Children's Cancer Institute, Sydney, New South Wales, Australia
  3. St. Vincent's Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, Australia
  4. School of Women's and Children's Health, Faculty of Medicine, UNSW, Sydney, NSW, Australia
  5. Centre for Single Cell Technology, School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Sydeney, NSW, Australia

Background: Breast cancer is one of the most common malignancies worldwide. Despite the success of the current treatments for specific subtypes of breast cancer, there are still no targeted options for patients diagnosed with triple-negative subtype (TNBC). Although immunotherapies have improved the clinical outcomes in other cancer types, they fail to produce benefits in TNBC. This failure has been attributed to the presence of an immunosuppressive microenvironment. Myeloid-derived suppressor cells (MDSCs) are a highly heterogeneous immune population with potent immunosuppressive functions that play an active role in the development of metastasis, the primary cause of death in TNBC patients. Targeting MDSCs thus presents an attractive and innovative therapeutic strategy to improve the efficacy and get better response rates in immunotherapy. However, due to the heterogeneous nature of MDSCs, the biggest challenge remains how to selectively target them. Understanding the specific molecular features that define MDSCs will open the possibility to implement new therapeutic strategies to improve the clinical outcomes of breast cancer patients

Methods: Using a single cell transcriptomic (scRNAseq) and epigenomic (scATACseq) approach, where we interrogate two different timepoints (pre-metastatic niche formation and metastasis), at two different tumour locations (primary tumour and lungs) in two different preclinical mouse models of breast cancer (the metastatic 4T1.2 and the non-metastatic 67NR), we aim to better define MDSC and unravel the inflammatory mechanisms that these cells employ to drive metastatic spread

Results: In this project, we have generated a temporal and spatial single-cell RNAseq and scATACseq map of TNBC in mouse models, where we deep characterize the myeloid lineage structure from the primary tumours and lung metastasis, and identify the pro-metastatic MDSC subpopulation and their malignant activation.

Conclusions: This study set up the first stone to identify and target the pro-metastatic MDSCs to combat TNBC.