Programmed death receptor-1/programmed death-ligand 1 inhibitors: Clinical progress and biomarker exploration in gastric cancer

Abstract

Gastric cancer is one of the most common malignant tumours, with limited treatment options and poor prognosis in its advanced stages. In recent years, breakthroughs in tumour immunotherapy have led to immune checkpoint inhibitors becoming a new class of clinical oncology drugs. Programmed death receptor-1 (PD-1) and programmed death-ligand 1 (PD-L1) play significant roles in inhibiting T cell responses and tumour immune escape. PD-1/PD-L1 inhibitors can significantly improve the prognosis of patients with advanced gastric cancer. Moreover, the combination of administering PD-1/PD-L1 inhibitors along with chemotherapy, radiotherapy, targeted therapy, and other immunotherapies may further enhance therapeutic efficacy. However, some scientific issues need to be urgently resolved in the immunotherapy of gastric cancer, including the suboptimal efficacy of PD-1/PD-L1 inhibitor monotherapy, high incidence of immune-related adverse events, and the absence of definitive biomarkers for effectively screening treatment-sensitive populations. This article reviews the mechanism of action, therapeutic advances, adverse effects, and putative predictive biomarkers of PD-1/PD-L1 inhibitors in the treatment of advanced gastric cancer.

Keywords: Gastric cancer; Immune checkpoint inhibitors; Immunotherapy; Programmed death receptor-1; Programmed death-ligand 1.

Fig. 1

Model of the interaction between programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in gastric cancer. PD-1 combines with its ligand PD-L1, resulting in T-cell inhibition and immune evasion. PD-1/PD-L1 inhibitors function by binding to either PD-1 or PD-L1, thereby blocking the PD-1:PD-L1 interaction, which allows T cells to regain their activity. The T cell receptor (TCR) recognizes antigens presented by the major histocompatibility complex (MHC), leading to the activation of T cells, which is the first step in initiating an immune response.