Applications of Circulating Tumor DNA in Immune Checkpoint Inhibition: Emerging Roles and Future Perspectives.

Chang Lu,Qing Zhou,Zhi-Hong Chen,Yi-Chen Zhang,Yi-Long Wu

doi:10.3389/fonc.2022.836891

Abstract

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.

Highlights

Immune checkpoint inhibitors (ICI), especially anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) antibodies, have been widely used as an effective therapy for many types of cancer, with impressive long-lasting responses in patients with non-small cell lung cancer (NSCLC) [1–3]
We summarize the implementation of circulating tumor DNA (ctDNA) in the context of ICI treatment in patients with NSCLC
Plasma ctDNA levels have been correlated with tumor burden and may promptly and accurately assess clinical responses and disease progression in response to ICI treatment [47, 52]

Summary

Introduction

Immune checkpoint inhibitors (ICI), especially anti-PD-1/PD-L1 antibodies, have been widely used as an effective therapy for many types of cancer, with impressive long-lasting responses in patients with non-small cell lung cancer (NSCLC) [1–3]. We discuss the utility of early on-treatment (usually within 8 weeks after treatment initiation) and extended monitoring, as well as the potential of plasma ctDNA to be used as a possible adjunct to radiographic assessment, among studies that utilize noninvasive biomarkers for long-term longitudinal monitoring response to checkpoint blockade and prediction of the risk of eventual progression.

Results

Conclusion