# Characterisation of Cytotoxicity-Related Receptors on γδ T Cells in Chronic Lymphocytic Leukaemia

## TL;DR

This study explores how γδ T cells in chronic lymphocytic leukemia patients show altered expression of cytotoxicity-related receptors, which may impact disease progression and treatment strategies.

## Contribution

The study identifies specific receptor expression patterns on γδ T cells in CLL patients, linking them to disease markers and suggesting anti-LAG-3 therapy as a potential treatment.

## Key findings

- CLL patients showed higher CD56 and LAG-3, and lower CD16 expression on γδ T cells compared to healthy controls.
- CD16 expression was inversely correlated with serum LDH levels, indicating a link to disease progression.
- Unmutated IGVH patients had higher HLA-DQA2 and HLA-DRB5 mRNA expression, suggesting a role in LAG-3 ligand interactions.

## Abstract

Chronic lymphocytic leukaemia (CLL) is a haematological malignancy primarily affecting older adults, characterised by the proliferation of functionally impaired B lymphocytes with abnormal expression of CD5, a typical T cell marker. The current study investigates the expression of cytotoxicity-related receptors (CD16, CD56, CD57, CD69) and a checkpoint (LAG-3) on γδ T cells in CLL patients. Sixty-nine treatment-naive CLL patients and fourteen healthy controls were recruited. Flow cytometry analysis revealed that the CLL patients had higher expressions of CD56 and LAG-3 and lower CD16 on their γδ T cells compared to the healthy controls. Subgroup analysis showed that ZAP-70-negative patients exhibited increased CD69, while CD38-negative patients showed higher CD16 expression. Additionally, CD16 expression was inversely correlated with serum LDH levels, a marker of disease progression. Bioinformatic analysis of the LAG-3 ligand mRNA in a CLL dataset indicated higher expression of HLA-DQA2 and HLA-DRB5 in patients with unmutated IGVH. Our findings highlight the altered expression of key cytotoxicity markers on γδ T cells in CLL, suggesting their potential role in disease progression and as a therapeutic target. In particular, the use of anti-LAG-3 antibodies seems promising.