Gene of the month: lymphocyte-activation gene 3 (LAG-3)

Lymphocyte-activation gene 3 (LAG-3) is a coreceptor found on activated T-lymphocytes activated B-lymphocytes and natural killer (NK) cells. It is closely related to CD4 where it shares multiple common and divergent features. It contains specific binding sites with high affinity to major histocompatibility complex (MHC) Class II and functions as an inhibitor of T-cell signalling. Tumour-infiltrating lymphocytes with high LAG-3 expression have been found in many solid tumours including ovarian cancer, melanoma, colorectal cancer and haematological malignancies including Hodgkin and diffuse large B-cell lymphoma. LAG-3 antagonism has been demonstrated to restore the anti-tumourigenic function of T-cells in vivo, however, mechanistic knowledge remains relatively poorly defined. As other immune checkpoint inhibitors have transformed the management of difficult to treat cancers, such as melanoma, it is hoped that LAG-3 might have the same potential. This review will explore LAG-3 modulation as an anticancer therapy, highlighting recent clinical developments.