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

High mobility group protein (HMGB1) is secreted by myeloid cells and cells of damaged tissues during inflammation, causing inflammatory reactions through various receptors, including TLR_S 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.