Predicting tumour evolution, immune surveillance and editing using integromic classification of the tumour microenvironment

Summary This project aims to identify tumour microenvironment signatures that predict immune-surveillance, immune-editing, tumour evolution and whether these signatures increase the risk of developing recurrence andor metastases.

Project Details

Colorectal cancer (CRC) is a biologically heterogeneous disease with distinct molecular subtypes defined by genomic and epigenomic changes that translate into divergent clinical outcomes1. CRC is also one of the most preventable cancers as it normally arises from benign neoplasms, and this polyp-tumour progression is a multistep process, likely occurring over many years2. There are currently four proposed theories of cancer evolution, however, all of these cancer evolution theories have a common theme, in that they are tumour cell-centric and do not consider the role of immune pressure from Darwinian selection. In recent years, the immune contexture within the tumour microenvironment (TiME) has been shown to have increasing importance for both tumour-promoting and tumour suppressive effects. Galon et al. has demonstrated in cohorts of primary CRCs that the phenotype, localisation and density of effector T cells was associated with prognosis, thus creating the Immunoscore3. What is currently lacking is an understanding of the interplay between tumour cells and immune cells and whether these temporal-spatial relationships determine the future behaviour of the tumour. This project aims to identify TiME signatures that depicts intra-tumoural heterogeneity, predicts immune-surveillance, immune-editing, and tumour evolution and whether these signatures increase the risk of developing recurrence and/or metastases.

Techniques : This project involves histopathological evaluation and genomic sequencing of colorectal polyps, cancers and paired metastasis samples to decipher the TiME involved with progression, local recurrence and metastasis. You will perform deep analysis of the TiME by immunohistochemistry, computational pathology, quantification and multi-plexed spectral imaging to understand the relationship between genomics and phenomics of the pre-malignant, primary CRC and paired recurrent lesions.