WEHI PhD Completion Seminar hosted by Professor Clare Scott

Imalki Kariyawasam
PhD Student – Scott Laboratory, Cancer division, WEHI

Characterising the Tumour Immune Microenvironment in Individuals with Multiple Primary Cancers

Davis Auditorium

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Including Q&A session

Please note this presentation will not be recorded

Multiple primary cancers (MPC) are defined when an individual develops more than one histologically or morphologically distinct cancer during their lifetime. The distinct cancers are not metastases of a previous cancer. Intriguingly, people with three or more primary cancers (3MP) have been shown to have significantly longer survival compared to people with a single cancer, similar to their age and sex matched controls. Although alterations in the genome can play a role in the development of multiple cancers in the same individual, we have seen that the majority of people with 3MP do not carry recognised germline pathogenic variants in cancer predisposition genes.

To characterise the tumour microenvironment (TME), we employed an integrated multi-omics approach comprising genomic analysis, panel-based transcriptome profiling of formalin-fixed paraffin-embedded (FFPE) tissue, plasma-based cytokine/chemokine immunoassays and spatial imaging technology using OPAL multiplex immunofluorescence. Because individuals with 3MP can develop any type of cancer (pan-cancer), we first developed and validated our analytical framework in a more homogeneous cohort: pre-treatment samples from the SOLACE2 clinical trial of PARP inhibitor and immunotherapy in high-grade serous ovarian cancer (HGSOC), enabling optimisation of methods against a single histological cancer type.

Within the SOLACE2 cohort, we integrated transcriptomic and imaging data to resolve the abundance, distribution, and interactions of key immune cell populations within the TME, relating these features to treatment response and disease progression, as well as circulating immunity, in order to provide a spatially informed view of immune dynamics in HGSOC. Subsequently we applied a similar multi-modal framework to the 3MP cohort, enabling us to identify differentially expressed genes, dysregulated signaling pathways, circulating cytokine/chemokine profiles, and abundance of immune cell infiltration which distinguish the 3MP group from other control cohorts. Together, these findings define a distinct TME immunophenotype that may underlie the uniqueness of cases with 3MP, generating testable hypotheses about the immunological mechanisms of cancer control for future validation.

All welcome!