The Multiple Potential Biomarkers for Predicting Immunotherapy Response—Finding the Needle in the Haystack

SIMPLE SUMMARY: There have been significant advances in the treatment of cancer within the past 10 years. Immunotherapy is a new type of treatment which uses the body’s own immune system to fight cancer. In some cancers, including lung, melanoma, bladder and kidney, immunotherapy has shown the potential to make people with advanced/metastatic disease live longer. However, most people do not derive any benefit from immunotherapy treatment, and the treatment may cause potentially serious side effects. Currently, our ability to correctly choose who should start these treatments and who is likely to benefit is limited because we do not have many tests to help us make this decision. A number of tests (also known as biomarkers) from tumour tissue, blood and the microbiome have shown promising results. These will be discussed in this review article. ABSTRACT: Immune checkpoint inhibitors (ICIs) are being increasingly utilised in a variety of advanced malignancies. Despite promising outcomes in certain patients, the majority will not derive benefit and are at risk of potentially serious immune-related adverse events (irAEs). The development of predictive biomarkers is therefore critical to personalise treatments and improve outcomes. A number of biomarkers have shown promising results, including from tumour (programmed cell death ligand 1 (PD-L1), tumour mutational burden (TMB), stimulator of interferon genes (STING) and apoptosis-associated speck-like protein containing a CARD (ASC)), from blood (peripheral blood mononuclear cells (PBMCs), circulating tumour DNA (ctDNA), exosomes, cytokines and metal chelators) and finally the microbiome.