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High Mobility Group Box 1 (HMGB1) Induces Toll-Like Receptor 4-Mediated Production of the Immunosuppressive Protein Galectin-9 in Human Cancer Cells

Teo Hansen Selnø, Anette, Schlichtner, Stephanie, Yasinska, Inna M., Sakhnevych, Svetlana S., Fiedler, Walter, Wellbrock, Jasmin, Berger, Steffen M., Klenova, Elena, Gibbs, Bernhard F, Fasler-Kan, Elizaveta, and others. (2021) High Mobility Group Box 1 (HMGB1) Induces Toll-Like Receptor 4-Mediated Production of the Immunosuppressive Protein Galectin-9 in Human Cancer Cells. Frontiers in Immunology, 12 . Article Number 675731. E-ISSN 1664-3224. (doi:10.3389/fimmu.2021.675731) (KAR id:90457)

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High mobility group box 1 (HMGB1) is a non-histone protein which is predominantly localised in the cell nucleus. However, stressed, dying, injured or dead cells can release this protein into the extracellular matrix passively. In addition, HMGB1 release was observed in cancer and immune cells where this process can be triggered by various endogenous as well as exogenous stimuli. Importantly, released HMGB1 acts as a so-called “danger signal” and could impact on the ability of cancer cells to escape host immune surveillance. However, the molecular mechanisms underlying the functional role of HMGB1 in determining the capability of human cancer cells to evade immune attack remain unclear. Here we report that the involvement of HMGB1 in anti-cancer immune evasion is determined by Toll-like receptor (TLR) 4, which recognises HMGB1 as a ligand. We found that HGMB1 induces TLR4-mediated production of transforming growth factor beta type 1 (TGF-β), displaying autocrine/paracrine activities. TGF-β induces production of the immunosuppressive protein galectin-9 in cancer cells. In TLR4-positive cancer cells, HMGB1 triggers the formation of an autocrine loop which induces galectin-9 expression. In malignant cells lacking TLR4, the same effect could be triggered by HMGB1 indirectly through TLR4-expressing myeloid cells present in the tumour microenvironment (e. g. tumour-associated macrophages).

Item Type: Article
DOI/Identification number: 10.3389/fimmu.2021.675731
Uncontrolled keywords: galectin-9, TGF-beta 1, HMGB1 (high mobility group box 1), immune surveillance, Toll-like receptors
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Vadim Sumbayev
Date Deposited: 29 Sep 2021 13:41 UTC
Last Modified: 10 Dec 2022 06:05 UTC
Resource URI: (The current URI for this page, for reference purposes)
Sumbayev, Vadim V.:
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