Vessels that encapsulate tumour clusters vascular pattern in hepatocellular carcinoma

Liu, Ken; Dennis, Claude; Prince, David; Marsh‐Wakefield, Felix; Santhakumar, Cositha; Gamble, Jennifer R.; Strasser, Stephan; McCaughan, Geoffrey W.

doi:10.1016/j.jhepr.2023.100792

Cited by 7 publications

(1 citation statement)

References 70 publications

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“…Angiogenesis is also a key feature of HCC, wherein hypervascularisation and leaky vessels pose challenges to the cellular immune control of tumours and influences responses to various therapies 10–12 . Amongst many angiogenic factors, vascular endothelial growth factor A (VEGFA) has been identified as the key driver of neovascularisation in HCC, with tumour cells largely implicated in its production 13,14 .…”

Section: Introductionmentioning

confidence: 99%

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

Marsh-Wakefield,

Santhakumar,

Ferguson

et al. 2023

Preprint

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Background & Aims: Hepatocellular 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 & Results: Using 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. Conclusions: Cellular 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.

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