TREM-1 as a novel immunotherapeutic target to treat pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is highly aggressive with limited curative options, primarily surgical resection. However, only about 20% of the tumors are resectable at diagnosis. Immunotherapies have largely failed in PDAC due to its immunosuppressive tumor microenvironment (TME). This study explores the potential of triggering receptor expressed on myeloid cells 1 (TREM-1) activation in altering the TME and enhancing tumor immunity in PDAC. Using the Pan02 mouse model and single-cell RNA sequencing (scRNA-seq), we found that intra-tumoral TREM-1 activation significantly reduced Pan02 tumor growth, an effect absent in mice. Our findings indicate that TREM-1 activation shifts tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) toward a pro-inflammatory state, promoting antitumor immune responses. Additionally, we show that TREM-1 myeloid cells infiltrate human PDAC tissue. These results suggest that TREM-1 activation could reprogram the immunosuppressive TME, offering a promising strategy for PDAC treatment.