Activated Galectin‐9/Tim3 promotes Treg and suppresses Th1 effector function in chronic lymphocytic leukemia

Tim‐3 is a negative immunoregulator in anti‐tumor response, but its mechanism in chronic lymphocytic leukemia (CLL) is not yet clear. The aim of this study was to understand the role of Galectin‐9/Tim‐3 signaling pathway in the regulation of CD4+ T cell subsets in CLL patients. Flow cytometry results showed that the number of Treg cells obviously increased, and there was a significant Treg/Th17 imbalance in CLL patients. In addition, Tim‐3 overexpressed on the surface of Th1 and Treg cells in CLL patients. The levels of Galectin‐9 and IL‐10 were significantly elevated in patients of CLL, especially in stages of Binet B, and C. However, IFN‐γ decreased. Moreover, Galectin‐9 in CLL patients was positively correlated with the number of Tim‐3+ Treg cells and the level of IL‐10. Interestingly, when the Tim‐3/Galectin‐9 pathway was blocked in vitro, the level of IL‐10 in the culture supernatant of CD4+ T was significantly reduced, while the levels of IFN‐γ and TNF‐α were increased. After co‐culture with activated Th1 cells, the apoptosis of CLL cells was significantly increased, and this effect was reversed after treatment with Tim‐3+ Tregs. In summary, Galectin‐9/Tim‐3 are elevated in CLL and associated with disease progression. By the negative regulation of CD4+ T cells, activated Galectin‐9/Tim‐3 suppresses Th1 effector function and also promotes Treg to be involved in immune escape of CLL. This pathway might become the potential target of immunotherapy in CLL patients.