SY10-1 The emerging role of cell-free DNA as a biomarker for cancer immunotherapy

Abstract

Over the past decade, immunotherapeutic strategies that target immune-checkpoint proteins programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have transformed the treatment paradigm across varied types of cancer, including non-small cell lung cancer (NSCLC). Immune-checkpoint inhibitors (ICIs) have resulted in durable response and long-term survival in a subsets of patients with metastatic NSCLC. Unfortunately, only a small proportion of patients could benefit from ICI treatment. Therefore, it is crucial to identify biomarkers that can effectively predict the efficacy of ICIs. Circulating tumor DNA (ctDNA), due to its minimally invasive nature and tumor cell-derived genomic landscape, has shown a promising role in the management of patients receiving ICI treatment. Two important predictive biomarkers for ICIs, including tumor mutational burden (TMB) and microsatellite instability (MSI) have been demonstrated to be successfully assessed by analyzing ctDNA. Furthermore, quantitative ctDNA assessment before or during treatment is associated with tumor response in patients treated with ICIs. Dynamic monitoring ctDNA is also helpful to distinguish pseudoprogression from true progression during ICI treatment. Other applications of ctDNA in cancer immunotherapy are also currently being investigated, including detection of minimal residual disease, early detection of resistance to immunotherapy, tracking neoantigens by personalized ctDNA, epigenetics and transcriptomics analysis using ctDNA. In the future, integrating pre-treatment and on-treatment ctDNA and other immune biomarkers will be helpful for personalized immunotherapy.