Current Progress on Predictive Biomarkers for Response to Immune Checkpoint Inhibitors in Gastric Cancer: How to Maximize the Immunotherapeutic Benefit?

Gastric cancer is the fifth most prevalent cancer and the fourth leading cause of cancer death globally. Delayed diagnosis and pronounced histological and molecular variations increase the complexity and challenge of treatment. Pharmacotherapy, which for a long time was systemic chemotherapy based on 5-fluorouracil, is the mainstay of management for advanced gastric cancer. Trastuzumab and programmed cell death 1 (PD-1) inhibitors have altered the therapeutic landscape, contributing to noticeably prolonged survivorship in patients with metastatic gastric cancer. However, research has revealed that immunotherapy is only beneficial to some individuals. Biomarkers, such as programmed cell death ligand 1 (PD-L1), microsatellite instability (MSI), and tumor mutational load (TMB), have been shown to correlate with immune efficacy in numerous studies and are increasingly employed for the selection of patients most likely to respond to immunotherapy. Gut microorganisms, genetic mutations like POLE/POLD1 and NOTCH4, tumor lymphoid infiltrating cells (TILs), and other novel biomarkers have the potential to develop into new predictors. Prospective immunotherapy for gastric cancer should be guided by a biomarker-driven precision management paradigm, and multidimensional or dynamic marker testing could be the way to go.