Previously, it was believed that the presence of an oncogenic mutation within a cell was sufficient to drive tumour development. However, it is now understood that tissues may contain cells harbouring oncogenic mutations, but that these cells maintain a normal phenotype until an initiating factor promotes oncogenic transformation (Acha-Sagredo et al, 2021). Changes in the cellular milieu and tissue architecture, such as inflammation or parenchymal density, are thought to alter the behaviour of these cells, affecting the likelihood of oncogenic transformation (Ling et al, 2020; Singh et al, 2019). Nonetheless, the precise mechanisms that underlie cancer promotion, and their association with factors such as smoking or obesity, are not fully understood.

With a unique worldwide cohort of 40 non-malignant kidney samples, we are using highly-multiplexed imaging to reveal crucial information about the tissue proteomic landscape, cellular composition and distribution, and changes in spatial architecture, to understand how these factors may promote oncogenic transformation. Additionally, we are analysing their association with known promoting factors, such as alcohol and smoking.

In these images, we are able to visualise the different functional compartments of the kidney, such as the different tubules (magenta, yellow, cyan) and glomeruli (dark blue), as well as immune cell infiltration and cellular milieu. On the left of the image, immune cells (green) can be seen infiltrating the tissue surrounding a fibrotic glomerulus (glomerulus in dark blue, periostin in red). The image displayed only shows a fraction of the total markers we have included in our panel, and downstream analysis will reveal detailed information about co-localisation of markers and cell-type clustering.

Overall, highly-multiplexed images provide a wealth of information about spatial architecture in tissues, that can be used to inform understanding of pathogenesis and disease prevention, and we are hoping to add these images to upcoming versions of the Human Protein Atlas.

This work is part of the Cancer Grand Challenges Prominent project. More information about this project can be found here.