Therapeutic Strategy and Resistance Mechanism of PD-L1 Monoclonal Antibody in Precision Population of Gastric Cancer

Abstract

PD-L1 is a core inhibitory immune checkpoint that finely regulates immune homeostasis. PD-L1 is closely linked to the pathogenesis of autoimmune diseases and malignant tumors, especially tumor immune escape, making it a pivotal target for cancer immunotherapy. This paper focuses on the biological functions of this immune checkpoint pathway, how to regulate the progression and metastasis of gastric cancer, and real-world use of PD-L1 monoclonal antibodies as well as their resistance mechanisms and safety profiles. Atezolizumab combined with chemotherapy or trastuzumab-based targeted therapy significantly improves the pathological complete response rate in gastric cancer patients. PD-L1 CPS ≥5 is an indicator used to judge the therapeutic effect. Durvalumab exhibits robust therapeutic benefits in neoadjuvant/adjuvant therapy, second-line treatment, and maintenance therapy for advanced gastric cancer, particularly in patients with high PD-L1 expression. Therapeutic resistance to PD-L1 inhibitors involves multiple factors including T-cell exhaustion, myeloid cell infiltration, exosomal PD-L1 secretion, and post-translational modifications of PD-L1. Immune-mediated toxicities arising from PD-L1 inhibitor therapy are manageable and not correlated with PD-L1 expression levels. This paper comprehensively summarizes the advances in PD-L1-targeted immunotherapy for gastric cancer, providing valuable insights for optimizing clinical treatment strategies and exploring novel solutions to overcome drug resistance.