ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Characterising the effect of Hck inhibition in a mouse mammary tumour model using single cell sequencing (#137)

Michael W Murrey 1 , Jay Steer 1 , Alistair Forrest 2 , Timo Lassmann 3 , David Joyce 1 , Fiona Pixley 1
  1. University of Western Australia, Nedlands, WA, Australia
  2. Harry Perkins Institute of Medical Research, Perth, WA
  3. Telethon Kids Institute, Perth

Macrophages are highly plastic cells that can adopt a variety of phenotypes, although they have been traditionally divided into “M1” inflammatory and “M2” wound healing macrophages. In tumours they display a mixed phenotype, where they are linked to a worse prognosis due to their growth, angiogenesis and invasion promoting capacity. As a result, targeting macrophages is likely to be beneficial in a variety of cancers. The effect of macrophage inhibition was investigated in an orthotopic mouse model of breast cancer using the PyMT mammary tumour derived Py8119 cell line. Inhibition of Hck, a Src family kinase highly expressed in macrophages and involved in macrophage motility, led to a 70% reduction in tumour growth. Using single cell RNAseq analysis and multiplex immunohistochemistry, we have characterised the immune landscape of treated and untreated Py8119 tumours to identify the mechanisms underpinning this striking decrease in growth. We found that tumour associated macrophages comprised the majority of immune cells in these tumours and can be grouped into three major populations (Cd74high, Cd206high and Chil3high clusters). Analysis of tumours treated with the Hck inhibitor, RK-20449, reveals significant changes in gene expression within the macrophage clusters. Tumour associated macrophages are a promising target and further insight into their behaviour in cancer may lead to novel therapies