Using gene expression to predict successful responses to chemoimmunotherapy

Nowak AK, Lesterhuis JW, Forrest A, Cook AM (2019-2021).

Funding: Mesothelioma Applied Research Foundation.

Synopsis (lay): We recently completed a clinical trial testing the combination of chemotherapy and a type of immunotherapy, known as ‘checkpoint blockade’, to treat malignant mesothelioma. The trial worked well for some people, but less well for others; the drugs can also have bad side-effects, and are very expensive. We collected small pieces of tumour from each patient shortly before they began treatment, which will give us a lot of detail about what was happening inside those tumours at that exact time. We predict that we will find common differences between people who received a benefit from the drug combination, and those who did not. If so, we can help patients and their doctors make an informed choice on whether these drugs are likely to benefit them – and maybe even find new ways to improve the number of people for whom the drugs will be successful.

Synopsis (scientific): Checkpoint blockade immunotherapies such as anti-PD-L1 antibody have proved highly effective in a variety of cancers, but only in a minority of patients. Our completed DREAM phase II trial, combining chemotherapy with Durvalumab (anti-PD-L1) immunotherapy, shows objective responses in 58% of those treated.  This project will complement the DREAM study by identifying biomarkers of response and non-response, through focussed analysis of gene expression. NanoString technology has the unique advantage that it can determine the expression of up to 770 immune-related genes from paraffin-imbedded tissue, to assay 24 immune cell types plus their activation status. We will apply this technology to pre-treatment tumour biopsies from all 54 patients who were treated in the DREAM trial. This will give us valuable detail on the gene expression profiles plus differentially expressed individual transcripts that could serve as potential future biomarkers in the chemo-immunotherapeutic treatment of mesothelioma.

NCARD Research Team