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Innate Sensing in the Tumour Microenvironment and Clinical Trials- Parkes Group

  • Parkes Group

Investigating Inflammatory Pathways in Cancer

Our lab is dedicated to understanding the complex interplay between cancer and the immune system, with a particular focus on intrinsic inflammatory pathways. These pathways, which serve as emergency response mechanisms to viral infections, can be hijacked by tumours to drive growth, invasion, and metastasis. By elucidating how these pathways are rewired in cancer, we aim to uncover new therapeutic targets to overcome immune evasion and resistance to treatment.

A major area of our research is understanding resistance mechanisms to immune-targeting therapies. Immunotherapies have revolutionised cancer treatment, yet many patients either do not respond or develop resistance over time. Our lab investigates how chromosomal instability (CIN) and DNA repair deficiency influence immune activation, tumour progression, and response to treatment. CIN is a hallmark of many aggressive cancers, leading to genetic chaos that can both stimulate and suppress immune responses. By dissecting the mechanisms through which CIN modulates immune signalling, we aim to develop strategies to enhance the efficacy of existing immunotherapies.

In recent work, we have identified a novel mechanism in gastro-oesophageal cancer where activation of the cyclic GMP-AMP synthase (cGAS) pathway paradoxically drives an immunosuppressive tumour microenvironment. While cGAS is typically associated with immune activation through STING (Stimulator of Interferon Genes) signalling, our findings suggest that in certain tumour contexts, this pathway can be co-opted to promote immune evasion. Understanding the molecular underpinnings of this process opens up opportunities for targeted interventions to reprogram the tumour microenvironment and restore anti-tumour immunity.

Another key focus of the Parkes Lab is the regulation of STING signalling in cancer, particularly at the endoplasmic reticulum (ER). STING is a critical mediator of innate immune responses, and its activation is tightly regulated to balance immune defence and prevent excessive inflammation. Tumours frequently exploit this regulatory machinery to dampen STING activity and evade immune surveillance. By dissecting the post-translational modifications, protein-protein interactions, and cellular trafficking pathways that govern STING function, we aim to identify novel therapeutic strategies to restore immune activation in cancer.

Beyond immune signalling, our lab is deeply invested in understanding the tumour microenvironment, including the role of fibroblasts and the extracellular matrix in shaping immune responses. Fibroblasts are key players in cancer progression, capable of creating an immunosuppressive niche that supports tumour survival and therapy resistance. By integrating cutting-edge techniques, including single-cell sequencing and spatial transcriptomics, we seek to unravel the cellular crosstalk within the tumour stroma and identify vulnerabilities that can be exploited for therapeutic benefit.

To tackle these pressing questions, we employ a multidisciplinary approach that spans in vitro cell models, in vivo tumour models, and ex vivo patient-derived organoids and samples. This comprehensive strategy enables us to bridge fundamental cancer biology with clinically relevant insights, ultimately driving the development of more effective cancer treatments.

The Parkes Lab is committed to pushing the boundaries of cancer research, with the goal of translating our discoveries into meaningful advances for patients. By uncovering the molecular intricacies of immune dysregulation in cancer, we hope to pave the way for novel immunotherapies that can overcome resistance and improve patient outcomes.

Our team

Latest publications