Immune checkpoint inhibitor therapy for gastric cancer: current status, therapeutic challenges, and future prospects

Gastric cancer is among the most prevalent malignant tumors of the digestive system worldwide. In recent years, immune checkpoint inhibitors (ICIs) have achieved substantial advances in the treatment of gastric cancer. By blocking the PD-1/PD-L1 and CTLA-4 signaling pathways, ICIs enhance antitumor immune responses and offer novel therapeutic options for patients. However, their clinical application continues to face significant challenges, including therapeutic resistance, immune-related adverse events, the lack of reliable biomarkers, and an immunosuppressive tumor microenvironment. This narrative review summarizes recent advances in ICIs-based therapies for gastric cancer, provides an in-depth analysis of existing clinical challenges, and highlights key future research directions, including biomarker discovery, development of predictive models, optimization of combination regimens, targeting of resistance mechanisms, modulation of the tumor-associated microbiota, and improved toxicity management. Moving forward, efforts should focus on advancing immunotherapy toward individualized and precision-based approaches to maximize both efficacy and safety, thereby enabling further optimization and breakthroughs in gastric cancer immunotherapy.