Enhanced Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) and Soluble TREM-1 Levels in the Myeloid Cells of Tumor-Bearing Mice and Patients with Renal Cell Carcinoma (100.8)

Abstract

Abstract Myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) contribute to cancer-related inflammation and tumor progression. TREM-1 amplifies the innate immune response and is thus emerging as an important player in inflammation and disease. Soluble TREM-1 (sTREM-1) is found in plasma of those with various inflammatory conditions and is associated with disease progression. Because TREM-1 is expressed on myeloid cells in healthy donors, we predicted TREM-1 would be expressed on MDSC and TAM within tumors and sTREM-1 would be elevated in the periphery. In this study, we examined TREM-1 and sTREM-1 levels in mice and patients with cancer. Using the 4T1 tumor model, we found that TREM-1 was present on blood and splenic MDSC in tumor-bearing mice and that levels increased over time after tumor challenge. TREM-1 was expressed on MDSC and TAM in the tumor. Ligation of TREM-1 on MDSC enhanced TNF release, indicating that the TREM-1 is functional. sTREM-1 was elevated in plasma of tumor-bearing mice and correlated with tumor volume. In renal cell carcinoma patients, TREM-1 was expressed on both tumor-infiltrating monocytes and neutrophils and plasma sTREM-1 levels increased with cancer stage. Taken together, these data show that TREM-1/sTREM-1 is regulated during tumor development, define TREM-1 as a novel MDSC marker, and demonstrate that TREM-1 on MDSC is functional. Future studies are needed to determine if TREM-1 can modulate tumor-associated inflammation.