The Tim-3-Galectin-9 Pathway and Its Regulatory Mechanisms in Human Breast Cancer

Yasinska, Inna M.; Sakhnevych, Svetlana S.; Pavlova, Ludmila; Hansen Selnø, Anette Teo; Teuscher Abeleira, Ana Maria; Benlaouer, Ouafa; Gonçalves Silva, Isabel; Mosimann, Marianne; Varani, Luca; Bardelli, Marco; Hussain, Rohanah; Siligardi, Giuliano; Cholewa, Dietmar; Berger, Steffen M.; Gibbs, Bernhard F.; Ushkaryov, Yuri A.; Fasler-Kan, Elizaveta; Klenova, Elena; Sumbayev, Vadim V.

doi:10.3389/fimmu.2019.01594

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Journal article

The Tim-3-Galectin-9 Pathway and Its Regulatory Mechanisms in Human Breast Cancer

Yasinska, Inna M. Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
Sakhnevych, Svetlana S. Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
Pavlova, Ludmila School of Biological Sciences, University of Essex, United Kingdom
Hansen Selnø, Anette Teo Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
Teuscher Abeleira, Ana Maria Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland - Zentrum Für Medizinische Bildung, Biomedizinische Analytik HF, Switzerland
Benlaouer, Ouafa Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
Gonçalves Silva, Isabel Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
Mosimann, Marianne Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland - Zentrum Für Medizinische Bildung, Biomedizinische Analytik HF, Switzerland
Varani, Luca Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Bardelli, Marco Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Hussain, Rohanah Beamline B23, Diamond Light Source, United Kingdom
Siligardi, Giuliano Beamline B23, Diamond Light Source, United Kingdom
Cholewa, Dietmar Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland
Berger, Steffen M. Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland
Gibbs, Bernhard F. Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom - Division of Experimental Allergology and Immunodermatology, University of Oldenburg, Germany
Ushkaryov, Yuri A. Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
Fasler-Kan, Elizaveta Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland - Department of Biomedicine, University Hospital Basel and University of Basel, Switzerland
Klenova, Elena School of Biological Sciences, University of Essex, Colchester, United Kingdom
Sumbayev, Vadim V. Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom

11.07.2019

Published in:

Frontiers in immunology. - 2019, vol. 10, p. 1594

English 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.

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