Immune exclusion in colorectal cancer (CRC) occurs at the very earliest stages of carcinogenesis. However recent studies have shown that for mismatch repair deficient CRC and a subset of mismatch proficient CRC immune checkpoint inhibition may have patient benefit. Therefore, the purpose of this project is to determine whether resistance to immune checkpoint inhibition is impacted by immune exclusion.
We will investigate the mechanisms which underpin immune cell exclusion from both primary tumour and liver metastasis in colorectal cancer in vivo, using organoids, mouse models, human tumour tissue and computational approaches. The project will focus upon KRAS mutant colorectal cancer, where there are currently no effective targeted therapeutic approaches, and will examine how epithelial-stroma-immune cell interactions lead to immune exclusion. We use novel approaches to increase immunogenicity of tumours, allowing us to examine whether this impacts immune exclusion, and finally whether increased immunogenicity and/or increased immune cell infiltration drives sensitivity to immune checkpoint inhibition in vivo.
We will perform spatially resolved multiplex imaging using tissue sections from mouse models and patient samples of CRC to reveal spatial components of immune exclusion. We will develop novel computational approaches to quantitatively characterise spatial neighbourhoods and communities of epithelial, stromal, and immune cells, allowing us to identify similarities and variations of spatial cell communities among different subsets and stages of colorectal cancers, and to uncover associations of cell community features with sensitivity and resistance to immune checkpoint inhibition.
About us
The CRUK Beatson Institute where the lab is based is a world leading cancer research institute, situated in the vibrant city of Glasgow in Scotland and hosting approximately 60 doctoral researchers at any one time. It has an excellent reputation for fundamental cancer research, including world-class metabolism studies and renowned in vivo modelling of tumour growth and metastasis.
To apply, and for further details on the application process, please click ‘Institute website’. Please do not email your CV.
References
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