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B23-Circular Dichroism	The Tim-3-Galectin-9 pathway and its regulatory mechanisms in human breast cancer Inna M. Yasinska , Svetlana S. Sakhnevych , Ludmila Pavlova , Anette Teo Hansen Selnø , Ana Maria Teuscher Abeleira , Ouafa Benlaouer , Isabel Gonçalves Silva , Marianne Mosimann , Luca Varani , Marco Bardelli , Rohanah Hussain , Giuliano Siligardi , Dietmar Cholewa , Steffen M. Berger , Bernhard F. Gibbs , Yuri A. Ushkaryov , Elizaveta Fasler-Kan , Elena Klenova , Vadim V. Sumbayev Frontiers In Immunology 10 DOI: 10.3389/fimmu.2019.01594 Diamond Proposal Number(s): [20755] Open Access Show Abstract ▼ Abstract: Human cancer cells operate a variety of effective molecular and signaling mechanisms which allow them to escape host immune surveillance and thus progress the disease. We have recently reported that the immune receptor Tim-3 and its natural ligand galectin-9 are involved in the immune escape of human acute myeloid leukemia (AML) cells. These cells use the neuronal receptor latrophilin 1 (LPHN1) and its ligand fibronectin leucine rich transmembrane protein 3 (FLRT3, and possibly other ligands) to trigger the pathway. We hypothesized that the Tim-3-galectin-9 pathway may be involved in the immune escape of cancer cells of different origins. We found that studied breast tumors expressed significantly higher levels of both galectin-9 and Tim-3 compared to healthy breast tissues of the same patients and that these proteins were co-localized. Increased levels of LPHN2 and expressions of LPHN3 as well as FLRT3 were also detected in breast tumor cells. Activation of this pathway facilitated the translocation of galectin-9 onto the tumor cell surface, however no secretion of galectin-9 by tumor cells was observed. Surface-based galectin-9 was able to protect breast carcinoma cells against cytotoxic T cell-induced death. Furthermore, we found that cell lines from brain, colorectal, kidney, blood/mast cell, liver, prostate, lung, and skin cancers expressed detectable amounts of both Tim-3 and galectin-9 proteins. The majority of cell lines expressed one of the LPHN isoforms and FLRT3. We conclude that the Tim-3-galectin-9 pathway is operated by a wide range of human cancer cells and is possibly involved in prevention of anti-tumor immunity.	Jul 2019

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B23-Circular Dichroism

The Tim-3-Galectin-9 pathway and its regulatory mechanisms in human breast cancer