PD-L1 as a Biomarker in Gastric Cancer Immunotherapy

Combining chemotherapy with immune checkpoint inhibitors (ICIs) that target the programmed death-1 (PD-1) protein has been shown to be a clinically effective first-line treatment for human epidermal growth factor receptor 2 (HER2)-negative and -positive advanced or metastatic gastric cancer (GC). Currently, PD-1 inhibitors combined with chemotherapy are the standard treatment for patients with HER2-negative/positive locally advanced or metastatic GC. Programmed death-ligand 1 (PD-L1) expression, as assessed using immunohistochemistry (IHC), is a crucial biomarker for predicting response to anti-PD-1/PD-L1 agents in various solid tumors, including GC. In GC, the PD-L1 IHC test serves as a companion or complementary diagnostic test for immunotherapy, and an accurate interpretation of PD-L1 status is essential for selecting patients who may benefit from immunotherapy. However, PD-L1 IHC testing presents several challenges that limit its reliability as a biomarker for immunotherapy. In this review, we provide an overview of the current practices of immunotherapy and PD-L1 testing in GC. In addition, we discuss the clinical challenges associated with PD-L1 testing and its future use as a biomarker for immunotherapy. Finally, we present prospective biomarkers currently under investigation as alternative predictors of immunotherapy response in GC.