Progress of immune checkpoint LAG-3 in immunotherapy

Immune checkpoint inhibition has been shown to successfully reactivate T cell responses directed against tumor-associated antigens, resulting in significantly prolonged overall survival in patients with various types of solid tumors. Among them, cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) play key roles in tumor immune escape and are well-established targets of cancer immunotherapy. However, the low response rate PD-1 and CTLA-4 is a limitation and a challenge. Hence, studies have focused on investigating the tumor microenvironment for alternative therapeutic targets. Lymphocyte activation gene 3 protein (LAG-3) negatively regulates T lymphocytes by binding to the extracellular domain of the ligand, thus avoiding autoimmunity caused by T cell overactivation. LAG-3 is an important immune checkpoint in vivo and plays a balanced regulatory role in the human immune system. LAG-3 is now regarded as a new generation of immunotherapy targets. The present review describes the research progress of LAG-3 to provide reference for further investigation of LAG-3. The immune checkpoint of LAG-3 plays a crucial role in cancer development and may be used in future clinical practice of cancer therapy.