LAG-3 is expressed on a majority of tumor infiltrating lymphocytes in pediatric Hodgkin lymphoma

Leuk Lymphoma. 2021 Mar;62(3):606-613. doi: 10.1080/10428194.2020.1839651. Epub 2020 Oct 28.

Abstract

LAG-3, through interaction with a variety of ligands, regulates T cell function via inhibition of T cell proliferation and activation. It has been demonstrated to be overexpressed on tumor infiltrating lymphocytes (TILs) of a variety of cancers with associated poor outcomes. The purpose of this study is to characterize the expression pattern and clinical significance of LAG-3 in pediatric Hodgkin lymphoma (HL). Patient tumor samples from Children's Oncology Group clinical trial AHOD0031 with matched patient outcome data were analyzed for the expression of LAG-3 and PD-L1 using immunohistochemistry. 73/115 patients (63%) demonstrated positive LAG-3 staining. No demographic or survival outcome data were significantly associated with LAG-3 expression. Interestingly, patients with the lowest density of expression were found to have the worst EFS, and those with highest density of expression demonstrated the best EFS. There was a positive statistically significant relationship between presence of LAG-3 and PD-L1 expression. This project is innovative in its characterization of LAG-3 as an immune checkpoint target in pediatric HL.

Keywords: LAG-3; Pediatric Hodgkin lymphoma; immune checkpoint; immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • B7-H1 Antigen / genetics
  • Child
  • Hodgkin Disease*
  • Humans
  • Immunohistochemistry
  • Lymphocyte Activation Gene 3 Protein
  • Lymphocytes, Tumor-Infiltrating
  • Lymphoma*
  • Programmed Cell Death 1 Receptor

Substances

  • Antigens, CD
  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human