Characterising tumour and immunological heterogeneity in colorectal cancer I Carolyn Shembrey

Transcriptomic, spatial and functional characterisation of tumour and immunological heterogeneity in colorectal cancer.

CAROLYN SHEMBREY
PhD Student,  Tumour Heterogeneity in Metastatic Cancer
University of Melbourne Centre for Cancer Research and Department of Clinical Pathology 

Intra-tumoural natural killer (NK) cells have emerged as a strong positive prognostic marker in colorectal cancer (CRC), suggesting that the next immunotherapy advance could come from harnessing this cellular compartment. However, the inter-patient variability of NK cell involvement in CRC is poorly characterised and very little is known regarding the influence of tumour heterogeneity on immunotherapy response.

In Carolyn’s thesis, the scope of tumour and immunological heterogeneity in CRC was assessed from transcriptomic, spatial and functional perspectives. A CRC-specific NK cell gene signature was used to infer the NK cell load in primary CRC tumours. Tumours with strong evidence of this NK cell signature were characterised by the upregulation of chemotactic and cytolytic transcriptional programs, and patients with high ‘NK scores’ were shown to have prolonged survival outcomes. Moreover, using a novel multiplex IHC panel to quantify the scope of NK cell infiltration and NK cell ligand expression, it was determined that neoadjuvant chemotherapy increased NK cell penetrance of metastatic CRC tissue. Collectively, this work has aided in identifying the molecular and clinical correlates of NK cell infiltration in CRC, potentially informing patient selection for NK cell-directed immunotherapies.

Carolyn Shembrey has submitted her PhD thesis through the Department of Clinical Pathology, The University of Melbourne Centre for Cancer Research. By combining traditional wet-lab approaches with computational biology, she aimed to interrogate the extent of natural killer cell involvement in metastatic colorectal cancer liver metastases and determine whether particular patient characteristics could be harnessed for innate immunotherapy.