Expression of Galectin-۹-related immune checkpoint receptors in B-cell acute lymphoblastic leukemia

Objective(s): Exhausted CD۸+ T-cells over-express immune checkpoint receptors (ICRs), which interact with their ligands on malignant cells. However, some ICRs have been reported to be expressed on both T-cells and tumor cells, including V-domain immunoglobulin suppressor of T cell activation (VISTA), Galectin-۹, and T-cell immunoglobulin mucin-۳ (TIM-۳). We aimed to evaluate the mRNA expression of VISTA, Galectin-۹, and TIM-۳ on CD۸+ T-cells and leukemic cells in B-cell acute lymphoblastic leukemia (B-ALL).Materials and Methods: Samples were obtained from ۲۶ untreated B-ALL patients and ۲۵ control subjects. CD۸+ T-cells were isolated using Magnetic Activated Cell Sorting (MACS). Relative gene expression was then evaluated by qRT-PCR with specific primers for VISTA, Galectin-۹, and TIM-۳. Also, the mRNA expression profile and clinical data of ۱۵۴ B-ALL patients were obtained from the TARGET.Results: mRNA expression of Galectin-۹ on CD۸+ T-cells in B-ALL patients was significantly lower than those in the control group (P=۰.۰۴۳), while VISTA expression was not significantly different between the two study groups (P=۰.۲۵۹). Besides, TIM-۳ expression was significantly higher in B-ALL patients than in the control group (P<۰.۰۰۱). Also, data obtained from TARGET showed that the relapse incidence was not significantly different between patients with high and low expression of Galectin-۹ and TIM-۳ in leukemic cells (P=۰.۳۶۰ and P=۰.۶۵۵, respectively).Conclusion: Collectively, gene expression results suggest an important role for TIM-۳, but not VISTA and Galectin-۹, in B-ALL and it seems that TIM-۳ could be a candidate for immune checkpoint therapy.

Keywords:

Acute lymphoblastic - leukemia , Gelectin-۹ , HAVCR۲ , Immune checkpoint - receptor , T-cell exhaustion , TIM-۳ , VISTA