# Association of Galectin-9 Soluble Immune Checkpoint with Clinical Prognostic Markers in Patients with Chronic Lymphocytic Leukemia

## TL;DR

This study found that galectin-9, a soluble immune checkpoint, is linked to clinical markers in chronic lymphocytic leukemia patients, suggesting its potential as a prognostic tool.

## Contribution

The study is the first to validate galectin-9 as a prognostic marker in chronic lymphocytic leukemia.

## Key findings

- Plasma levels of sCD25, TIM-3, galectin-9, PD-1, and PD-L1 were significantly higher in CLL patients than in controls.
- Galectin-9 levels were directly associated with β2-microglobulin levels in CLL patients.
- Galectin-9 shows potential as a valuable prognostic marker for CLL.

## Abstract

Chronic lymphocytic leukemia (CLL) is a heterogenous disease, with varied clinical outcomes. Multiplex assays used to measure soluble immune checkpoints offer a less laborious method of monitoring patients with CLL, but none of these panels have been validated. The aim of the study was to assess soluble immune checkpoint profiles in patients with CLL and to correlate these with independent prognostic markers such as β2-microglobulin (B2M), Rai stage, fluorescence in situ hybridization (FISH) status, and the International Prognostic Index for Chronic Lymphocytic Leukemia (CLL-IPI). We measured plasma levels of soluble interleukin-2 receptor alpha (sCD25), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), galectin-9, programmed cell death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) using cytometric bead array-based assays. We further measured plasma levels of B2M using an enzyme-linked immunosorbent assay (ELISA) kit. Soluble immune checkpoints were correlated with prognostic markers. The plasma levels of sCD25, TIM-3, galectin-9, PD-1, and PD-L1 were significantly increased in patients with CLL compared to the control group, p < 0.0001. Galectin-9 plasma levels were directly associated with B2M levels (β = 0.65, p = 0.012). Our findings suggest that galectin-9 may provide valuable prognostic significance for patients with CLL.