PhD. student National Yang Ming Chiao Tung University Taipei, Taipei, Taiwan
Abstract Text: Tumor-associated macrophages (TAMs) can modify T cell activity through antigen presentation and cytokine secretion within the tumor microenvironment. M1-polarized macrophages can activate cytotoxic T cells and initiate tumor immune surveillance. Triggering receptor expressed on myeloid cells 1 (Trem1) is explicitly expressed on TAMs, and its signaling pathway enhances inflammatory responses and promotes macrophage M1 polarization. However, it is unclear how Trem1-mediated responses activate T cell responses and regulate tumor growth. Our recent research demonstrated that Trem1 plays a role in presenting tumor antigens to T cells, which helps eliminate tumors. We conducted investigations using Trem1 knockout (KO) mice and found that Trem1 has a significant anti-tumor function in the tumor microenvironment. Using the BioID assay, we discovered a new Trem1 ligand from necrotic tumor cells that can activate Trem1-mediated responses as an agonist. According to surface plasmon resonance, the binding affinity between the ligand and Trem1 is approximately KD=5.99E-8, indicating a high binding affinity. The mechanisms of the findings suggest that the novel Trem1 ligands promote Trem1-Dap12-mediated endocytosis, leading to the phosphorylation of Tyrosine-protein kinase (SYK) and enhancing tumor-antigen presentation, which in turn activates tumor-specific T cells. In addition, we generated a recombinant soluble form of the Trem1 ligand and observed its capacity to induce tumor elimination in a Trem1-dependent manner. The study shows the potential of using soluble Trem1 ligands for tumor therapy through a Trem1-mediated anti-tumor mechanism.
