Gonçalves Silva Isabel, Rüegg Laura, Gibbs Bernhard F, Bardelli Marco, Fruehwirth Alexander, Varani Luca, Berger Steffen M, Fasler-Kan Elizaveta, Sumbayev Vadim V
School of Pharmacy, University of Kent , Canterbury, United Kingdom.
Institute for Research in Biomedicine, Universita' della Svizzera italiana (USI) , Bellinzona, Switzerland.
Oncoimmunology. 2016 Jun 29;5(7):e1195535. doi: 10.1080/2162402X.2016.1195535. eCollection 2016 Jul.
The immune receptor Tim-3 is often highly expressed in human acute myeloid leukemia (AML) cells where it acts as a growth factor and inflammatory receptor. Recently, it has been demonstrated that Tim-3 forms an autocrine loop with its natural ligand galectin-9 in human AML cells. However, the pathophysiological functions of Tim-3 in human AML cells remain unclear. Here, we report for the first time that Tim-3 is required for galectin-9 secretion in human AML cells. However, this effect is cell-type specific and was found so far to be applicable only to myeloid (and not, for example, lymphoid) leukemia cells. We concluded that AML cells might use Tim-3 as a trafficker for the secretion of galectin-9 which can then be possibly used to impair the anticancer activities of cytotoxic T cells and natural killer (NK) cells.
免疫受体Tim-3在人类急性髓系白血病(AML)细胞中通常高度表达,在这些细胞中它作为一种生长因子和炎症受体发挥作用。最近,已经证明Tim-3在人类AML细胞中与其天然配体半乳糖凝集素-9形成自分泌环。然而,Tim-3在人类AML细胞中的病理生理功能仍不清楚。在此,我们首次报道Tim-3是人类AML细胞中半乳糖凝集素-9分泌所必需的。然而,这种作用具有细胞类型特异性,到目前为止发现仅适用于髓系(而非例如淋巴系)白血病细胞。我们得出结论,AML细胞可能利用Tim-3作为分泌半乳糖凝集素-9的转运分子,然后半乳糖凝集素-9可能被用于削弱细胞毒性T细胞和自然杀伤(NK)细胞的抗癌活性。