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Gene of the month
Gene of the month: lymphocyte-activation gene 3 (LAG-3)
  1. Mark P Lythgoe1,
  2. Daniel Si Kit Liu1,
  3. Nicola E Annels2,
  4. Jonathan Krell1,
  5. Adam Enver Frampton1,2,3
  1. 1Department of Surgery and Cancer, Imperial College London, London, UK
  2. 2Department of Clinical and Experimental Medicine, University of Surrey, Faculty of Health and Medical Sciences, Guildford, Surrey, UK
  3. 3HPB Surgical Unit, Royal Surrey NHS Foundation Trust, Guildford, UK
  1. Correspondence to Adam Enver Frampton, Department of Surgery and Cancer, Imperial College London, London, UK; a.frampton{at}imperial.ac.uk

Abstract

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.

  • lymphocytes
  • biomarkers
  • tumor
  • medical oncology
  • chemotherapy
  • cancer
  • regional perfusion

https://doi.org/10.1136/jclinpath-2021-207517

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    Footnotes

    • Handling editor Runjan Chetty.

    • Twitter @mlythoe

    • MPL and DSKL contributed equally.

    • Contributors Conception or design: MPL and DSKL. Acquisition, analysis or interpretation of data: MPL and DSKL. Drafting the work or revising it critically for important intellectual content: NEA, AEF and JK. Final approval of the version to be published: MPL, DSKL, NEA, JK and AEF.

    • Funding This study was funded by Royal College of Surgeons of England.

    • Competing interests JK has received honoraria from Clovis Oncology, Tesaro and AstraZeneca, outside the submitted work. None of the aforementioned companies had any input into the study design, data collection, reporting or preparation of the manuscript.

    • Provenance and peer review Commissioned; internally peer reviewed.