Expression of Galectin-9-related immune checkpoint receptors in B-cell acute lymphoblastic leukemia

Document Type : Original Article


1 Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

2 Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran

3 Department of Biostatistics and Epidemiology, Mazandaran University of Medical Sciences, Sari, Iran

4 Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran

5 Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

6 Department of Hematology and Oncology, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran

7 Thalassemia Research Center (TRC), Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran


Objective(s): Exhausted CD8+ 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-9, and T-cell immunoglobulin mucin-3 (TIM-3). We aimed to evaluate the mRNA expression of VISTA, Galectin-9, and TIM-3 on CD8+ T-cells and leukemic cells in B-cell acute lymphoblastic leukemia (B-ALL).
Materials and Methods: Samples were obtained from 26 untreated B-ALL patients and 25 control subjects. CD8+ 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-9, and TIM-3. Also, the mRNA expression profile and clinical data of 154 B-ALL patients were obtained from the TARGET.
Results: mRNA expression of Galectin-9 on CD8+ T-cells in B-ALL patients was significantly lower than those in the control group (P=0.043), while VISTA expression was not significantly different between the two study groups (P=0.259). Besides, TIM-3 expression was significantly higher in B-ALL patients than in the control group (P<0.001). Also, data obtained from TARGET showed that the relapse incidence was not significantly different between patients with high and low expression of Galectin-9 and TIM-3 in leukemic cells (P=0.360 and P=0.655, respectively).
Conclusion: Collectively, gene expression results suggest an important role for TIM-3, but not VISTA and Galectin-9, in B-ALL and it seems that TIM-3 could be a candidate for immune checkpoint therapy.


Main Subjects

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