DRG2 as a Biomarker to Enhance the Predictive Efficacy of PD-L1 Immunohistochemistry Assays

PD-L1 immunohistochemistry (IHC) assays are used as a companion diagnostic for immunotherapy with immune checkpoint inhibitors (ICIs). However, despite the association between PD-L1 expression and clinical benefit from ICIs, the PD-L1 IHC assay is not sufficiently accurate in predicting response to ICIs; some patients with high PD-L1 expression do not respond to ICIs. Recently, researchers provided insights into why some patients with high PD-L1 expression fail to respond to ICIs. They discovered that DRG2 is a critical regulator of PD-L1 endosomal trafficking in cancer cells, which is essential for the proper localization of PD-L1 on the cell surface. Although DRG2-depleted cells express high levels of PD-L1 and are PD-L1 IHC-positive, the PD-L1 sequestered in early endosomes does not respond to ICIs. Therefore, a companion diagnostic combining DRG2 expression with a PD-L1 IHC assay may improve the therapeutic response to PD-1/PD-L1 ICIs.