The application of immune checkpoint inhibitors has proven to be an effective treatment for cancer. Immune checkpoints such as programmed cell death protein 1/programmed cell death protein 1 ligand 1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T-cell immunoglobulin-3 (TIM-3), T-cell immunoglobulin and ITIM domain (TIGIT), and lymphocyte activation gene-3 (LAG-3) have received extensive attention, and the efficacy of antibodies or inhibitors against these checkpoints (either alone or in combination) has been evaluated in many tumors. This paper provides a brief overview of the PD-1 and LAG-3 checkpoints, and then shifts focus to the combined use of PD-1 and LAG-3 antibodies in both in vivo and in vitro experiments. In the in vitro experiments, we examined the correlation between the expression and activation of these inhibitors on T cells, and also assessed toxicity in animals in preparation for in vivo experiments. The effects of the combined use of PD-1 and LAG-3 antibodies were then summarized in animal models of melanoma, MC38 carcinoma, and other tumors. In clinical studies, the combined application of these antibodies was assessed in patients with melanoma, colorectal, breast, and renal cell cancers, as well as other solid tumors. In general, the combination of PD-1 and LAG-3 antibodies has shown promising results in both in vivo and in vitro studies.

In recent years, the immunotherapy of gastric cancer has made a breakthrough. With the emergence of immune checkpoint inhibitors, blocking the inhibitory molecules in the body can reactivate the immune system to resist tumors, which dramatically improves the survival rate of gastric cancer patients. Lymphocyte activation gene-3 (LAG-3), also known as CD223, is a kind of immune checkpoint receptor protein, mainly expressed in activated immune cells, and it has the functions of maintaining internal environment stability and immunological regulation and is closely related to the occurrence and development of tumor. Therefore, LAG-3 can be used as a new target for tumor immunotherapy. In this narrative review, the structure, immunological function, and research progress of immune checkpoint LAG-3 in gastric cancer is explored to provide a reference for further research and immunotherapy of gastric cancer.