Dama P, et al. - In a phase I dose escalation trial enrolling Acute Myeloid Leukemia (AML) patients, researchers studied immune checkpoint pathways active in these patients, particularly during the course of remission induction chemotherapy, with a focus on T cell immunoglobulin and mucin domain 3 (TIM-3)/Gal-9 (additional negative regulatory pathway in promoting T cell exhaustion). As induction therapy, Selinexor [a Selective Inhibitor of Nuclear Export] was combined with high-dose cytarabine and mitoxantrone (NCT02573363). Patients with treatment failure (TF) vs those in complete remission exhibited a significantly higher frequency of Gal9⁺ CD34⁻ cells, compared to baseline, and a correlation of this finding with increased TIM-3 expression on marrow-resident T cells was found in TF patients. Moreover, analysis of bone marrow samples vs peripheral blood for the expression level of PD-1 and TIM-3 revealed a significantly higher TIM-3 in bone marrow specimens. In AML patients, the probability of complete remission could be increased effectively by targeting the Gal9/Tim-3 axis in combination with induction chemotherapy.