Genes & Cancer

The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy

Long Long1,2, Xue Zhang1, Fuchun Chen3, Qi Pan3, Pronnaphat Phiphatwatchara1, Yuyang Zeng1 and Honglei Chen1

1 Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, P. R. China

2 Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, P. R. China

3 Department of Thoracosurgery, Traditional Chinese Medical Hospital of Wenling, Wenling, Zhejiang, China


Honglei Chen, email:

Keywords: immune checkpoint; lymphocyte activation gene-3; cancer immunotherapy; tumor microenvironment

Received: August 13, 2018 Accepted: September 16, 2018 Published: September 23, 2018


Cancer immunotherapy and tumor microenvironment have been at the forefront of research over the past decades. Targeting immune checkpoints especially programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) has made a breakthrough in treating advanced malignancies. However, the low response rate brings a daunting challenge, changing the focus to dig deeply into the tumor microenvironment for alternative therapeutic targets. Strikingly, the inhibitory immune checkpoint lymphocyte activation gene-3 (LAG-3) holds considerable potential. LAG-3 suppresses T cells activation and cytokines secretion, thereby ensuring immune homeostasis. It exerts differential inhibitory impacts on various types of lymphocytes and shows a remarkable synergy with PD-1 to inhibit immune responses. Targeting LAG-3 immunotherapy is moving forward in active clinical trials, and combination immunotherapy of anti-LAG-3 and anti-PD-1 has shown exciting efficacy in fighting PD-1 resistance. Herein, we shed light on the significance of LAG-3 in the tumor microenvironment, highlight its role to regulate different lymphocytes, interplay with other immune checkpoints especially PD-1, and emphasize new advances in LAG-3-targeted immunotherapy.

PII: 180