PD1/PDL1 and TIM3/Gal9 expression in acute lymphoblastic leukemia: Gal-9 expression on leukemia stem cells as an independent prognostic parameter.

The introduction of immune checkpoint inhibitors (ICI) which are designed not to activate the immune system to attack tumors but to eliminate the inhibitory signals that block antitumor T-cell responses represents a breakthrough in the treatment of malignancies. However, studies in acute lymphoblastic leukemia (ALL) patients are scarce in number and in the parameters addressed. In the present study we investigated the expression of two ICI inhibitors, PD1 and TIM3 on BM T- lymphocytes and PDL1 and Gal9 on blast cells and leukemia stem cells (LSCs) in 85 newly diagnosed ALL patients using flow cytometry. The associations and correlations with different clinical and hematological parameters were investigated. The results revealed that higher expression of these markers is associated with poor prognostic parameters in some instances and good prognostic parameters in others. These findings indicate that different prognostic parameters may have different mechanisms of action. The results of Gal9 expression on LSCs are notable. Gal9 expression on LSCs was negatively correlated with the percentage of LSCs% (r=-0.414, P < 0.001) indicating that both the number and the biological characteristics of LSCs should be considered. Additionally, Low Gal9 expression on LSCs was an independent prognostic parameter for both OS (p = 0.016) and PFS (p = 0.034). This finding has not been previously reported. In conclusion this work represents a comprehensive study of some ICIs in ALL. The expression of Gal9 on LCSs may be a potential candidate for targeted therapy.