The immuno-genomic landscape of cancers
During tumour development, cancer cells continuously acquire mutations that can also give rise to neoantigens, novel cancer-specific peptides presented on the cell surface eliciting a host immune response. Cells that display strongly immunogenic neoantigens are more likely to be eliminated by the immune system, hence neoantigens are associated with a negative selection pressure. In many cancers, however, tumour-associated immune activity is inhibited by genetic alterations in (neo)antigen presentation or modulation of the tumour microenvironment.
We combine mathematical modelling and bioinformatic evaluation of neoantigens and immune escape to investigate the genetic and epigenetic changes introduced by the tumour-immune interaction.
Previous work
In work up to date, we/I
- Co-developed a python-based neoantigen prediction pipeline, NeoPredPipe.
- Created a stochastic model of neoantigen accummulation in growing tumours to study their evolution. We identified the pattern of immune-induced negative selection in the clone size (or variant allele frequency) distribution of cancers.
- Evaluated immunogenic properties of a large cohort of colorectal cancers (100,000 Genomes Project), and quantified the effect of immune escape mutations.
- Modelled the evolutionary advantage arising from mutation rate evolution in mismatch repair-deficient cancers.
- Investigated the when and how of immune evasion using the spatially resolved multi-omic dataset of the Evolutionary Predictions in Colorectal Cancer cohort. We found early (clonal) genetic alterations and epigenome regulation to define the cancer-immune interaction that stays fairly stable in later tumour growth.
Current and future interests
Our (non-exhaustive) list of interests include
- Expanding our existing models to explore how the clone size of neoantigens or spatial distribution of mutations affects tumour evolution under immune selection
- Uncovering the impact of therapy on the cancer-immune interaction - in particular, how therapy-induced and -selected mutations alter this interaction
- Modelling how intracellular abundances and processes contribute to (neo)antigen surface presentation and immune response.
- Investigating how aneuploidy and non-genetic alterations can modulate neoantigen-induced immunogenicity.
- Understanding dynamical properties of the cancer-immune interaction from imaging data and agent-based models.