Mechanistic insight of predictive biomarkers for antitumor PD-1/PD-L1 blockade: A paradigm shift towards immunome evaluation

Checkpoint inhibitor-based immunotherapy has exhibited unprecedented success in the treatment of advanced-stage cancer in recent years. Several therapeutic antibodies targeting programmed death-1 (PD-1) or its ligand (PD-L1) have received regulatory approvals for the treatment of multiple malignancies, including melanoma, non-small cell lung cancer, kidney cancer and Hodgkin's lymphoma. However, a substantial proportion of patients still do not benefit from these agents, let alone the risk of immune-associated toxicities and financial burden. Therefore, it is imperative to identify valid predictive biomarkers which can help optimize the selection of patients. In this review, a mechanism-based interpretation of tumor PD-L1 expression and other candidate biomarkers of response to antitumor PD-1/PD-L1 blockade was provided, particularly for the tumor microenvironment-derived ‘immunomes’, and the challenges faced in their clinical use was addressed. Directions for future biomarker development and the potential of combined biomarker strategies were also proposed.