Gonçalves Silva, Isabel Yasinska, Inna M. Sakhnevych, Svetlana S. Fiedler, Walter Wellbrock, Jasmin Bardelli, Marco Varani, Luca Hussain, Rohanah Siligardi, Giulio Ceccone, Giacomo Berger, Steffen M. Ushkaryov, Yuri A. Gibbs, Bernhard F. Fasler-Kan, Elizaveta Sumbayev, Vadim V. 2017-07-19 Acute myeloid leukemia (AML) is a severe and often fatal systemic malignancy. Malignant cells are capable of escaping host immune surveillance by inactivating cytotoxic lymphoid cells. In this work we discovered a fundamental molecular pathway, which includes ligand-dependent activation of ectopically expressed latrophilin 1 and possibly other G-protein coupled receptors leading to increased translation and exocytosis of the immune receptor Tim-3 and its ligand galectin-9. This occurs in a protein kinase C and mTOR (mammalian target of rapamycin)-dependent manner. Tim-3 participates in galectin-9 secretion and is also released in a free soluble form. Galectin-9 impairs the anti-cancer activity of cytotoxic lymphoid cells including natural killer (NK) cells. Soluble Tim-3 prevents secretion of interleukin-2 (IL-2) required for the activation of cytotoxic lymphoid cells. These results were validated in ex vivo experiments using primary samples from AML patients. This pathway provides reliable targets for both highly specific diagnosis and immune therapy of AML. application/pdf https://susi.usi.ch/global/documents/319087 https://n2t.net/ark:/12658/srd1319087 https://susi.usi.ch/documents/319087/files/goncalves_silva_ebiom_2017.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ebiom.2017.07.018 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319087 info:eu-repo/semantics/openAccess CC BY-NC-ND Ebiomedicine. - 2017, vol. 22, p. 44-57 Acute myeloid leukemia Tim-3 Galectin-9 NK cells Anti-leukemia immunity info:eu-repo/classification/udc/61 The tim-3-galectin-9 secretory pathway is involved in the immune escape of human acute myeloid leukemia cells http://purl.org/coar/resource_type/c_6501