Progress of immune checkpoint LAG‑3 in immunotherapy (Review)
Chanchan Shan, Xing Li, Jian Zhang
Abstract
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 <em>in vivo</em> 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.