Driving tumor-associated macrophages to a CXCL9Hi/SPP1Low phenotype eliminates pancreatic cancer

Recent studies have revealed the complex PDAC microenvironment, which fosters interactions between various cell types that contribute to immunosuppression. Among these, tumor-associated myeloid cells with a CXCL9-low, SPP1-high phenotype are particularly abundant and play a significant role in promoting disease progression.

We hypothesized that targeting these cells could reprogram the tumor microenvironment and improve survival outcomes. To test this, we developed a novel myeloid cell-targeting nanoformulation, CANDI470, designed to increase CXCL9 expression and reduce SPP1 levels in tumor-associated myeloid cells. Our results demonstrate that this approach not only enhances immune responses but also leads to remarkable therapeutic efficacy, including cures in murine PDAC models, even when used as a monotherapy.