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

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:

• Pediatric Hodgkin lymphoma
• LAG-3
• immune checkpoint
• immunotherapy

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The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This project was supported by funds from the St. Baldrick’s Foundation and the Children’s Oncology Group Foundation NCTN ITSC-Hematopoietic Malignancies Grant UG1CA233249. Protocol AHOD0031 was supported by National Cancer Institute Grant no. U10 CA98543, NCTN Operations Center Grant U10CA180886 and NCTN Statistics & Data Center Grant U10CA180899 to the Children's Oncology Group Chair.