WEHI PhD Completion Seminar hosted by Professor Jane Visvader

Shirley Song

PhD Student – Lindeman/Visvader Laboratory, ACRF Cancer Biology & Stem Cells division – Cancer Research and Treatments  Theme, WEHI

Investigating the immune microenvironment during breast cancer development and understanding invasive lobular breast cancer

Davis Auditorium

Join via SLIDO enter code #WEHIphdcompletion

Including Q&A session

Followed by refreshments in Tapestry Lounge

Breast cancer is the leading cause of cancer-related death in women worldwide and its profound heterogeneity is manifest in multiple dimensions.

To interrogate the role played by the immune microenvironment in breast tumorigenesis, the first part of my project developed two spectral flow cytometry panels to extensively characterise the immune microenvironment at the hyperplastic and tumour stages in five genetically engineered mouse models (GEMMs). The results showed drastic remodelling of immune composition and functional status in all tumours. Through exploiting single-cell RNA sequencing (scRNA-seq) and immunofluorescence confocal microscopy, we unveiled heterogeneity within myeloid antigen- presenting populations in tumours and distinct spatial distribution patterns between the myeloid subsets.

My second aim focuses on further understanding the immune microenvironment and potential cells of origin of invasive ductal breast cancer (IDC) and invasive lobular breast cancer (ILC), which are the two most common subtypes of breast cancer. These two subtypes diverge in histopathology, genetic landscape, metastasis and clinical outcome. To explore the differences between ER+ ILC and ER+ IDC, we utilised multiplex ion-beam imaging by time of flight (MIBI-TOF) and scRNA-seq to profile the tumour immune microenvironment. The results showed different immune compositions and diverse functional subsets in myeloid and T cell populations in the two groups of tumours. Furthermore, to trace the cells-of-origin of ILC, we established novel E-cadherin-loss mouse models driven by two lineage specific genes: Elf5 and Krt8. Tumours generated from the two models displayed distinct latencies and histological features. RNA sequencing analysis of epithelial subsets indicated potential tumorigenic pathways and heterogeneous transcriptomic profiles within tumours.

Overall, these projects generated valuable resources for understanding oncogenic mechanisms that contribute to breast cancer at the cellular and molecular levels, providing insights into both cancer cell-intrinsic aberrations and the extrinsic immune microenvironment.

All Welcome!