PD-L1 copy number gains: a predictive biomarker for PD-1/PD-L1 blockade therapy?

Immune checkpoint blockade has emerged as a promising and distinct treatment strategy and has caused a paradigm shift in oncology. Significant response and survival benefit have been observed in a fraction of patients who were treated with immune checkpoint inhibitors (ICIs) in several malignancies including melanoma (1-3), non-small-cell lung cancer (NSCLC) (4-7), gastric cancer (8), urothelial carcinoma (9), Hodgkin’s lymphoma (10), and head and neck squamous cell carcinoma (11). Additionally, because clinical response to ICI treatment has been seen to vary from to patient, a predictive marker that provides insight on patient response is urgently needed. Currently established companion diagnostics include the HercepTest？ immunohistochemistry (IHC) staining for breast and gastric cancers, fluorescence in situ hybridization (FISH) assays to disclose anaplastic lymphoma kinase (ALK) translocations for NSCLC, and mutation analyses for the epidermal growth factor receptor (EGFR) gene in NSCLC and BRAF for melanoma. Individual differences in treatment efficacy of ICIs may be due to the complex interaction of the tumor microenvironment; where tumor, immune, and stromal cells closely interact. Thus, it has been difficult to establish simple determinants that would predict the efficacy of ICIs like those currently used in targeted therapy