The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells

Sumbayev, Vadim V., Silva, Isabel Goncalves, Yasinska, Inna M., Sakhnevych, Svetlana S., Fiedler, Walter, Wellbrock, Jasmin, Bardelli, Marco, Varani, Luca, Hussain, Rohanah, Siligardi, Giuliano, and others. (2019) The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells. EBioMedicine, 22 . pp. 44-57. ISSN 2352-3964. E-ISSN 2352-3964. (doi:10.1016/j.ebiom.2017.07.018) (KAR id:63193)

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Official URL: https://doi.org/10.1016/j.ebiom.2017.07.018

Abstract

Acutemyeloid leukemia (AML) is a severe and often fatal systemicmalignancy. 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.

Item Type:	Article
DOI/Identification number:	10.1016/j.ebiom.2017.07.018
Uncontrolled keywords:	Acute myeloid leukemia; Anti-leukemia immunity; Galectin-9; NK cells; Tim-3, Medway School of Pharmacy
Subjects:	Q Science
Divisions:	Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User:	Vadim Sumbayev
Date Deposited:	01 Sep 2017 16:52 UTC
Last Modified:	05 Nov 2024 10:58 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/63193 (The current URI for this page, for reference purposes)

University of Kent Author Information

Sumbayev, Vadim V..

Creator's ORCID:	https://orcid.org/0000-0002-9404-5626
CReDIT Contributor Roles:

Ushkaryov, Yuri.

Creator's ORCID:	https://orcid.org/0000-0002-5712-8297
CReDIT Contributor Roles:

Gibbs, Bernhard F.

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