Liquid biomarkers for cancer immunotherapy.

Treatments that create or enhance anti-cancer immune responses have revolutionised the way that many cancers are treated and improved clinical outcomes. Yet many patients do not respond to treatment, and treatment-related side effects are common. Current methods to predict response and toxicity are very limited, meaning that many patients receive therapy that does not benefit them, and may cause harm. Better predictive biomarkers for immunotherapy are needed. Blood is an attractive specimen type in which to identify biomarkers as it is easy to obtain and can be sampled on multiple occasions throughout a patient’s treatment. Using patient cohorts and biospecimens collected via the Alfred Cancer Biobank, we are investigating the utility of novel chemical and cellular biomarkers in blood samples of patients receiving immunotherapy-based treatment. This project seeks to evaluate immune phenotypes, non-coding RNA (microRNA), hormones and metabolites (especially of dietary/microbial origin) as composite predictors of known clinical outcomes in patient cohorts from our clinics. Lung and skin cancers (melanoma or non-melanoma) are the primary current focus but may be extended to other cancer types of interest. These biomarker-based studies will be performed in close association with mechanistic evaluation using a variety of cellular, tumour-fragment culture and pre-clinical model systems, to determine potential causal associations with biomarkers of interest, and to incorporate these features into increasingly comprehensive molecular/cellular models of cancer immunotherapy response. A combination of wet lab techniques for biomarker analysis and evaluation, and statistical data analysis will be critical for these studies.