Immune checkpoint inhibitors (ICIs), especially anti-programmed death 1 (PD-1)/
programmed death ligand 1 (PD-L1)
antibodies, have made dramatic progress in the treatment of
lung cancer, especially for patients with
cancers not driven by oncogenes. However, responses are limited to a subset of patients, and which subset of patients will optimally benefit from ICI remains unknown. With the advantage of being minimally invasive and dynamic, noninvasive
biomarkers are promising candidates to predict response, monitor resistance, and track the evolution of
lung cancer during ICI treatment. In this review, we focus on the application of
circulating tumor DNA (ctDNA) in plasma in
immunotherapy. We examine the potential of pre- and on-treatment features of ctDNA as
biomarkers, and following multiparameter analysis, we determine the potential clinical value of integrating predictive liquid
biomarkers of ICIs to optimize patient management. We further discuss the role of ctDNA in monitoring treatment resistance, as well as challenges in clinical translation.