Tumour Inflammation and Immunotherapy

Inflammation triggered by uncontrolled activation of the innate immune system is associated with at least one third of all cancers (e.g. lung, stomach, pancreatic, colorectal, liver) highlighting the need to understand the molecular and cellular basis by which regulators of innate immunity drive certain cancers.

Immunotherapy has revolutionized the treatment landscape in cancer, yet many cancers remain refractory to current immunotherapy (such as with adaptive immune check point inhibitors).

Combinatorial and complementary approaches will be employed to:

1. Therapeutically enhance the visibility of certain tumour types to be attacked by the adaptive immune system (i.e. boost anti-tumour adaptive immunity), and
2. Identify inflammation-associated tumour types in which targeting the innate immune response suppresses tumour-promoting inflammation.

The cancer disease to be targeted is not defined, with a tissue agnostic approach, but encompasses all cancer.

Group Leader - Professor Brendan Jenkins

The pathogenesis of at least 25% of cancers (e.g. gastric, pancreatic, lung) is associated with chronic inflammation driven by over-activation of the body’s two arms of the immune system: innate immunity, a rapid, non-specific immune response against microbes and tissue injury that can persist long-term in a chronic state; and adaptive immunity, a slower, more specific immune response encompassing T cell-mediated and humoral immunity.  While harnessing the adaptive immune response via immunotherapy to treat cancers using immune checkpoint inhibitors and more recently, CAR-T cells, is established, intervention against innate immunity, despite its great potential, is understudied.  The work performed by our group aims to reveal molecular regulators of innate immunity as novel targets for anti-cancer therapy.

The projects undertaken in our group combine molecular biological and genetic approaches, together with human translational studies, to identify the mechanisms by which uncontrolled activation of key regulators of the innate immune system, namely pattern recognition receptors (PRRs) such as toll-like receptors (TLRs) and cytosolic DNA sensors, as well as inflammasomes, lead to inflammation-associated cancers of the stomach, lung and pancreas.  In addition, we investigate how the iRhom and ADAM17 families of proteases, as well as the interleukin (IL)-6 cytokine family, contribute to these innate immune-driven inflammation-associated cancers, potentially via crosstalk with PRRs. 

Our studies on the role of innate immunity in cancer are also complemented by our investigations into how the above-mentioned innate immune regulators trigger chronic inflammatory conditions which are risk factors for certain cancers.  In particular, our group focuses on chronic gastritis, pancreatitis and emphysema/COPD which can predispose individuals to gastric (stomach), pancreatic and lung cancers, respectively.