Tumour Immunology

Tumour Microenvironment

MRC ICASE PARTNERSHIP - Student Project:
Using oncolytic viral therapy to target the tumour microenvironment in chromosomally unstable cancers

Commercial partner Theolytics have identified and developed novel oncolytic viral therapeutics shortly entering the clinical setting. However, the behaviour of these therapeutic agents in a fibroblast-rich, immunosuppressed tumour microenvironment is not currently known and of key interest as these are typically cancers resistant to other immunotherapeutic approaches. In this project, using their lead therapeutic candidates, 2D and 3D co-culture models will be used to characterise the relationship between tumour cell characteristics, fibroblast phenotype and response to oncolytic viral therapy.

• Understand resistance mechanisms to immune-targeting treatments in cancer;
• Characterise the role of the interaction of chromosomal instability and DNA repair deficiency with immune activation in tumour initiation, progression and response.
• Study tumour microenvironment, fibroblasts and extracellular matrix in chromosomally unstable cancers.

In the Parkes Lab we study intrinsic inflammatory pathways in cancer. These are important immune pathways, present in all cells, that act as emergency response pathways to viral infection. However, in cancer, these pathways can be rewired and hijacked by the tumour to promote growth, invasion and metastasis.

Dr Parkes was the first to describe constitutive innate immune signalling in BRCA1/2 mutant cancers activating cGAS-STING signalling. This work has subsequently led to a clinical trial investigating a biomarker for BRCA1/2 deficiency in breast cancer, as well as interest in the action of STING agonists in BRCA1/2 mutant disease. Her work on ENPP1 and chromosomal instability identified a novel mechanism whereby cGAS-cGAMP-STING signalling can be subverted to result in tumour-mediated immunosuppression. She is an international expert on cGAS-STING signalling in cancer and the impact of this signalling on the tumour microenvironment.

Kathy Chan, Post-Doctoral Researcher

Su Phyu, Post-Doctoral Researcher

Bruno Beernaert, DPhil student

Matt Jackson, DPhil student

Jamie Kwon, DPhil student

Kay Shigemori, DPhil student

Ashley Jackson, MRes student

Subashan Vadibeler, MRes student

Tong Liu, Visiting researcher

Rebecca Sipthorpe (2020-2022), Research technician - Wellcome-funded PhD student at the University of Bristol