Poster Presentation 35th Lorne Cancer Conference 2023

Mechanisms of stromal-induced immunosuppression in triple negative breast cancer (#121)

Julia Chen 1 2 3 , Travis Ruan 2 3 , Sergio Erdal Irac 2 , Sunny Wu 4 , Elgene Lim 1 2 3 , Alex Swarbrick 2 3
  1. Department of Medical Oncology, St Vincent's Hospital, Darlinghurst, NSW, Australia
  2. Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW, Australia
  3. St Vincent Campus, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia
  4. Turley Lab, Immunology Discovery & Oncology Bioinformatics, Genentech, San Francisco, California, USA

Triple negative breast cancer (TNBC) accounts for 10-20% of breast cancers and carries a poor prognosis with limited treatment options. Immunotherapy with immune checkpoint inhibitors has been investigated as a potential treatment option in this disease, but few patients derive complete or durable responses from treatment. There is increasing evidence that stromal cells are important regulators of immune function in solid tumours and may contribute to the ability of tumours to evade anti-tumour response. However, the functional diversity of these cell within the tumour immune microenvironment and their exact mechanisms remain poorly explored in a clinical context.


We investigated the immunosuppressive capabilities of stromal cells in vitro by establishing ex vivo co-culture models of primary TNBC stromal cells and peripheral blood mononuclear cells (PBMCs), and used flow cytometry and single-cell RNA-seq (scRNAseq) to assess mechanisms of stromal-immune interactions. In our co-culture systems, PBMCs are stimulated and labelled with CSFE dye. When these are co-cultured with TNBC stromal cells, there is significant suppression of T cell proliferation seen in both CD4 and CD8 T cells. This is not HLA-dependent, as similar suppressive effects are seen in both HLA-matched and non-HLA-matched PBMCs. T cell proliferation is also suppressed when PBMCs are co-cultured with conditioned media, suggesting a secreted factor effect. scRNAseq of co-cultured PBMCs revealed upregulated expression of immune-inhibitory and T cell dysfunction markers. Our findings suggest that stromal cells suppress effective immune response and may be co-targeted to improve response to immunotherapy in TNBC.