The significance of galectin-9 and T-cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) in patients with chronic lymphocytic leukemia: The role of immune evasion.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a hematological malignancy with the accumulation of mature, monoclonal B lymphocytes. CLL cells can escape the host's immune response by inducing T-cell exhaustion. This occurs by upregulation of inhibitory checkpoint receptors, such as T-cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3). Galectin-9 (Gal-9) is a soluble ligand for TIM-3. Its interaction with TIM-3 can induce T-cell exhaustion in various cancers. Therefore, targeting these inhibitory pathways may be a potential therapy for CLL.

SUBJECTS& METHODS: This case-control study included 200 participants, divided into two groups. Group 1 included 100 treatment-naïve patients with newly diagnosed CLL. Group 2 (control group) included 100 age- and sex-matched healthy individuals. Gal-9 expression was estimated by real-time polymerase chain reaction, while flow cytometric %TIM-3+ on CD3+, CD3+CD4+, and CD3+CD8+ T cells was measured.

RESULTS: Galectin-9 mRNA expression and flow cytometric %TIM-3+ on CD3+, CD3+CD4+, and CD3+CD8+ T-cells were significantly higher in CLL patients than healthy controls. Both markers were significantly associated with prognostic markers (β2-microglobulin, lactate dehydrogenase (LDH), chromosomal abnormalities, and Rai stage).

CONCLUSION: Galectin-9/TIM-3 interaction has a possible role in the development and progression of CLL. Gal-9 mRNA expression and %TIM-3+ on CD3+, CD3+CD4+, and CD3+CD8+ T-cells are potential discriminators between CLL patients and healthy controls. This was demonstrated by high sensitivity and specificity. Additionally, they had significant correlations with prognostic markers, including β2-microglobulin, LDH, chromosomal abnormalities, CD38, and Rai stage.