Progress and Challenges of Predictive Biomarkers for Immune Checkpoint Blockade

Over the past decade, immune checkpoint blockade (ICB) therapy has revolutionized the outlook for oncology with significant and sustained improvement in the overall patient survival. Unlike traditional cancer therapies, which target the cancer cells directly, ICB acts on the immune system to enhance anti-tumoral immunity. However, the response rate is still far from satisfactory and most patients are refractory to such treatment. Unfortunately, the mechanisms underlying such heterogeneous responses between patients to ICB therapy remain unclear. In addition, escalating costs of cancer care and unnecessary immune-related adverse events also are pertinent considerations with applications of ICB. Given these issues, identifying explicit predictive biomarkers for patient selection is an urgent unmet need to increase the efficacy of ICB therapy. The markers can be classified as tumor related and non-tumor-related biomarkers. Although substantial efforts have been put into investigating various biomarkers, none of them has been found to be sufficient for effectively stratifying patients who may benefit from immunotherapy. The present write up is an attempt to review the various emerging clinically relevant biomarkers affecting the efficacy of immune checkpoint inhibitors, as well as the limitations associated with their clinical application.