The Interaction of HMGB1 with the Proinflammatory TREM-1 Receptor Generates Cytotoxic Lymphocytes Active against HLA-Negative Tumor Cells

Author:

Yurkina Daria M.1ORCID,Romanova Elena A.1,Feoktistov Alexey V.2,Soshnikova Natalia V.2ORCID,Tvorogova Anna V.3,Yashin Denis V.1,Sashchenko Lidia P.1

Affiliation:

1. Institute of Gene Biology (RAS), Moscow 119334, Russia

2. Engelhardt Institute of Molecular Biology (RAS), Moscow 119334, Russia

3. Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology (RAS), Moscow 119334, Russia

Abstract

High mobility group protein (HMGB1) is secreted by myeloid cells and cells of damaged tissues during inflammation, causing inflammatory reactions through various receptors, including TLRS and RAGE. TREM-1 is considered to be one of the potential HMGB1 receptors. In this work, we have shown that the HMGB1 protein is able to bind to the TREM-1 receptor at high affinity both in solution and on the cell surface. This binding causes lymphocytes to release cytokines IL-2, IL-1b, IL-6, TNF and Ifny into the medium, which leads to the appearance of cytotoxic lymphocytes in PBMC capable of lysing HLA-negative tumor cells. Expanding the spectra of proinflammatory receptor ligands and understanding the mechanisms of their action is essential for the creation of new immunotherapy pathways.

Funder

Ministry of Science and Higher Education Russian Federation

Publisher

MDPI AG

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