Iranian Journal of Basic Medical Sciences (Dec 2023)

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

  • Armin Akbar,
  • Hossein asgariyan-Omran,
  • Reza Valadan,
  • Mohammad-Mehdi Dindarloo,
  • Ahmad Najafi,
  • Amir Kahrizi,
  • Arash Poursheikhani,
  • Hossein Karami,
  • Mohammad Naderi,
  • Shayan Sabeti,
  • Mohsen Tehrani

DOI
https://doi.org/10.22038/ijbms.2023.73159.15901
Journal volume & issue
Vol. 26, no. 12
pp. 1468 – 1474

Abstract

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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.

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