MAY 19, 2020 11:15 AM EDT | APAC MAY 20, 2020 2:15 PM CST

A Multi-omic Single Cell and Spatial Atlas of Breast Cancer Reveals Stromal Suppression of Anti-Cancer Immunity

Speaker
  • Associate Professor of Medicine at UNSW Sydney, NHMRC Senior Research Fellow and co-head of the Breast Translational Oncology Program in the Kinghorn Cancer Center, Sydney
    Biography
      Alex graduated with a Bsc (Hons I) in Molecular and Cellular Biology from UNSW in 1995. After obtaining his PhD in 2003 he undertook postdoctoral training with Nobel laureate J. Michael Bishop at the University of California, San Francisco, supported by a CJ Martin Travelling Fellowship from the NHMRC.
      In 2008 Alex established the Tumour Progression Laboratory in the Garvan Institute and in 2012 was appointed co-Head of the Breast Translational Oncology Program in the newly commissioned Kinghorn Cancer Centre. Alex is an Associate Professor at UNSW and an NHMRC Senior Research Fellow.
      Alex is the convenor of the Lorne Cancer Conference, Australia's pre-eminent multi-disciplinary cancer research conference & the Australian Translational Breast & Prostate Cancer Symposium. He serves on the Cancer Research Committee of the Cancer Council NSW.

    Abstract

    We applied CITE-Seq to measure >150 cell surface immune markers and checkpoint proteins simultaneous to RNA-Sequencing. We resolve the tumour-immune milieu with high precision and reveal subsets of CD8 T cells that are specific to luminal and triple-negative breast cancers, with unique checkpoint molecule expression. In addition, a number of stromal cell-states were identified across the cohort, including three subsets of cancer-associated fibroblasts (CAFs), two subsets of smooth-muscle cells and four subsets of endothelial cells. Distinct transcription factor networks regulate these polarised states. We derived novel markers for these populations using CITE-Seq and carried out prospective isolation and functional characterisation of stromal subsets. Ligand-receptor signalling predicted a role for CAF subsets in T cell immunosuppression, which was further supported by deconvoution analysis of large bulk RNA_Seq cohorts and by in vitro CAF-T-cell co-culture proliferation assays.


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