Immunomodulatory Cancer Therapies

What we do

We study techniques that modify the immune response to tumours, with particular emphasis on hepatopancreatobiliary (HPB) cancers. Our current focus is defining the immunomodulatory mechanism of radiofrequency ablation (RFA) at a microscopic, cellular and molecular level, so that it can be used selectively as a primer for immunotherapy in pancreatic ductal adenocarcinoma (PDAC). Other immunogenic tumour priming techniques of interest include stereotactic radiotherapy and cryoablation.

Why it is important

The 5-year & 10-year survival of PDAC is ~3.5% and <1% making it almost universally fatal. Advances in surgery, peri-operative care and systemic chemotherapy have not significantly improved the prognosis of PDAC for several decades. Early clinical trials of immunotherapy have yielded disappointing results however there is evidence of mechanisms in the tumour microenvironment which serve to decrease the immune response, and it has been observed that immunogenic subtypes of pancreatic cancer carry a better prognosis. There is therefore an urgent need to address the systemic treatment of this aggressive disease.

How it can benefit patients

This research seeks to reveal new drug targets or combination treatments that improve the efficacy of therapy with direct translation to clinical trials. The experimental pipelines will be used to study other immunomodulatory treatments for a range of different solid tumours.

Summary of current research

• In vivo syngeneic models of PDAC and HCC are used to evaluate the clinical and molecular effect of RFA in combination with cytotoxic and immunotherapies
• Quantification of adaptive immune response in the tumour microenvironment using FACS and IHC
• Defining molecular subtype changes in the tumour using gene expression profiling (Nanostring) following immunomodulatory treatment
• Clinical translation – current trials include the ARDEO study (A phase II prospective randomised clinical study of endoscopic ultrasound guided radiofrequency ablation (EUS-RFA) for inoperable ductal pancreatic carcinoma)