RT Journal Article
SR Electronic
T1 Gene of the month: lymphocyte-activation gene 3 (LAG-3)
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 543
OP 547
DO 10.1136/jclinpath-2021-207517
VO 74
IS 9
A1 Mark P Lythgoe
A1 Daniel Si Kit Liu
A1 Nicola E Annels
A1 Jonathan Krell
A1 Adam Enver Frampton
YR 2021
UL http://jcp.bmj.com/content/74/9/543.abstract
AB 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.