Comprehensive overview of biomarkers to predict response to immune checkpoint therapy in lung cancer

Immune checkpoint (IC) therapy has brought a huge revolution in the field of lung cancer treatment over the past decade. It has also revolutionised treatment paradigm and has tremendously improved patient prognosis. IC inhibitors (ICIs) targeting Programmed Cell Death Protein 1/Programmed cell death Ligand 1 (PD1/PD-L1) have shown remarkable success and are now being used as first-line therapies in metastatic disease, adjuvant therapy following surgical resection and chemotherapy in resectable disease. Despite this remarkable success, only a subset of patients obtains complete benefit and most patients do not respond or develop progressive disease during treatment. ICIs are relatively expensive and some patients suffer from significant immune-related adverse toxicities. Hence, the identification and discovery of new predictive and prognostic immunotherapy biomarkers remains the present crucial need for patient selection, stratification and also for guiding therapeutic decisions. Currently established biomarkers such as PD-L1 determined by immunohistochemistry and tumour mutation burden determined by next-generation sequencing are non-specific and possess limitations. At present, several other biomarkers using peripheral blood, liquid biopsies along with gene expression signatures, and tumour infiltrating lymphocytes are being researched globally which have demonstrated predictive potential to characterise ICIs responders. In this review, we provide a comprehensive overview of the current biomarkers, highlighting the main clinical challenges and possible novel potential biomarkers to better predict responders to ICIs.