Poster Presentation 35th Lorne Cancer Conference 2023

Defining cancer associated fibroblast states associated with response to checkpoint immunotherapy in the triple negative breast cancer. (#167)

Sergio Erdal Irac 1 , Louise Baldwin 1 2 , Travis Ruan 1 2 , Julia Chen 1 3 , Alex Swarbrick 1 2
  1. Garvan Institute of Medical Research, Sydney, NSW, Australia
  2. School of Clinical Medicine, University of New South Wales, Sydeny, NSW, Australia
  3. The Kinghorn Cancer Centre, Sydney, NSW, Australia

Treatment of cancer has been revolutionised by immune checkpoint blockade, however the majority of patients have incomplete responses, particularly so in breast cancer. Despite the landscape of immune therapy most of the studies in this field are mainly focused on T cells and tumour cells, however it is becoming increasingly clear that other immune and non-immune cell types can modulate anti-cancer immunity.

We generated single cell RNA-Seq (scRNA-Seq) profiles from more than 250,000 cells harvested from 2 mouse models of triple negative breast cancer (TNBC) treated with single and combination checkpoint inhibitor therapy.  In additional we integrated scRNA-seq data from publicly available human TNBC neoadjuvant immunotherapy clinical trial testing either anti-PD-1 or anti-PD-1 combined with chemotherapy. We used these data to identify immune cell and cancer associated fibroblast (CAF) populations as potential mediators of cellular crosstalk in the tumor microenvironment. Furthermore, we identified changes in immune and CAF populations associated with response to therapy.  Parallel analysis of immune cell and CAF composition from mouse models and breast cancer patients using the Visium spatial transcriptomics platform provides orthogonal validation. Our comprehensive analysis of key CAF and immune cell subsets in human and mouse will identify cellular interactions regulating TNBC immunity and identify new candidates for CAF-targeted agents to enhance the efficacy of immunotherapies.