# Reed-Sternberg cells express CD161 and lectin-like transcript 1 in Hodgkin lymphoma

**Authors:** Anwar Rjoop, Rania Al-Samama'h, Laith Al-Eitan

PMC · DOI: 10.3389/fmed.2026.1754727 · Frontiers in Medicine · 2026-03-10

## TL;DR

This study finds that Reed-Sternberg cells in Hodgkin lymphoma express CD161 and LLT1, which could be useful for future immunotherapy treatments.

## Contribution

This is the first study to detect CD161 expression in Reed-Sternberg cells at the protein level.

## Key findings

- LLT1 expression in Reed-Sternberg cells is mainly cytoplasmic with occasional membranous expression.
- CD161 is expressed in Reed-Sternberg cells for the first time at the protein level.
- No significant association was found between LLT1/CD161 expression and clinical-pathological features like subtype or EBV status.

## Abstract

Hodgkin lymphoma (HL) is a B-cell lymphoma, and it is diagnosed by the presence of Reed-Sternberg (RS) cells surrounded by heavy immune cell infiltration in a tissue biopsy. CD161 (Cluster of differentiation 161) and its ligand Lectin-like transcript 1 (LLT1) have recently emerged as a novel immune-regulatory axis that modulates natural killer (NK) and T cell-mediated function in cancer and inflammatory conditions, but their expression in RS cells and association with HL patients' clinical-pathological features remain poorly defined.

In this study, 60 formalin-fixed paraffin-embedded (FFPE) tissue samples were collected from patients in Northern Jordan. In addition to 60 FFPE samples of positive control from benign reactive lymph node tissues and tonsils. Immunohistochemistry (IHC) was performed to assess the expression levels and patterns (cytoplasmic, membranous, or both) of CD161 and LLT1 in RS cells and then correlated with EBV status and clinical-pathological features such as subtype and disease stages.

LLT1 expression in RS cells was predominantly cytoplasmic, with occasional dual cytoplasmic and membranous expressions. This is the first study in the literature to detect CD161 expression in RS cells as neoplastic cells at protein level. Statistical analyses showed no significant association between LLT1 or CD161 expression in RS cells and HL subtype, stage or EBV status.

These findings provide the first characterization of LLT1 and CD161 expression in RS cells and suggest their potential use as a target in immunotherapy approaches in HL.

## Linked entities

- **Genes:** KLRB1 (killer cell lectin like receptor B1) [NCBI Gene 3820], CLEC2D (C-type lectin domain family 2 member D) [NCBI Gene 29121]
- **Diseases:** Hodgkin lymphoma (MONDO:0004952)

## Full-text entities

- **Genes:** CLEC2D (C-type lectin domain family 2 member D) [NCBI Gene 29121] {aka CLAX, LLT1, OCIL}
- **Diseases:** inflammatory (MESH:D007249), HL (MESH:D006689), B-cell lymphoma (MESH:D016393), Reed-Sternberg (MESH:C535516), cancer (MESH:D009369)
- **Chemicals:** formalin (MESH:D005557), paraffin (MESH:D010232)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC13008727/full.md

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13008727/full.md

## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC13008727/full.md

---
Source: https://tomesphere.com/paper/PMC13008727