Expression of Galectin-9-related immune checkpoint receptors in B-cell acute lymphoblastic leukemia
نویسندگان
1 Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
2 Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
3 Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran
4 Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
5 Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
6 Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran
7 Department of Hematology and Oncology, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
8 Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
9 Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran
10 Department of Biostatistics and Epidemiology, Mazandaran University of Medical Sciences, Sari, Iran
11 Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
doi
10.22038/ijbms.2023.73159.15901چکیده
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.
