Immunotherapy for gastric cancer: Advances and challenges

Gastric cancer (GC) ranks among the leading causes of cancer-related mortality globally. Often, its initial stages manifest subtly, and the infrequency of routine screenings contributes to late diagnoses in many cases. Systemic treatments for GC include chemotherapy, targeted therapy, and immunotherapy, among which immunotherapy is the first-line standard treatment for advanced GC. In recent years, immunotherapy has seen notable advancements, as evidenced by the Food and Drug Administration's approval of drugs such as nivolumab and pembrolizumab for GC treatment. Additionally, several other drugs are currently under rigorous preclinical and clinical investigation. This review aims to shed light on the recent advancements in immunotherapy for GC, particularly emphasizing the insights gained from phase 2/3 clinical trials that assess the efficacy, safety, and promise of various immunotherapeutic modalities, including immune checkpoint inhibitors, CAR-T-cell therapies, and cancer vaccines, in enhancing patient outcomes. Moreover, this review delves into the intricate immunological framework of GC, focusing on the tumor microenvironment, interactions among immune cells, and the roles of immune checkpoints such as PD-L1. We also address the hurdles and prospective paths forward in the realm of immunotherapy for GC, offering fresh viewpoints on potential therapeutic approaches in this evolving domain.