Spatial mapping of the hepatocellular carcinoma landscape identifies unique intratumoural perivascular-immune neighbourhoods

Abstract

AbstractBackground & AimsHepatocellular carcinoma (HCC) develops in the context of chronic inflammation, however, the opposing roles the immune system plays in both the development and control of tumours is not fully understood. Mapping immune cell interactions across the distinct tissue regions could provide greater insight into the role individual immune populations have within tumours.Approach & ResultsUsing highly multiplexed imaging mass cytometry, we have mapped the immune landscape of tumour, invasive margin, and adjacent non-tumour regions across sixteen resected tumours comprising of 144 regions of interest and over 10,000 parameters. We show immune cell densities remain largely consistent across these three regions, except for subsets of monocyte-derived macrophages which are enriched within the tumours. Mapping cellular interactions across these regions in an unbiased manner identifies immune neighbourhoods comprised of tissue-resident T cells, dendritic cells, and various macrophage populations around perivascular spaces. Importantly, we identify multiple immune cells within these neighbourhoods interacting with VEGF+perivascular macrophages.ConclusionsCellular interactions, but not cell densities, differ between intratumoural and adjacent non-tumour regions in HCC. Unique intratumoural immune neighbourhoods around the perivascular space points to an altered landscape within tumours. Enrichment of VEGF+perivascular macrophages within these tumours could play a key role in angiogenesis and vascular permeability.