Work

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

Year: 2026

Type: article

Abstract: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, with limited therapeutic options. Recent studies reveal 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 hypothesize that targeting these cells can reprogram the tumor microenvironment and improve survival outcomes. To test this, we develop a 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 achieves remarkable therapeutic efficacy, including cures in murine PDAC models, even when used as a monotherapy. This myeloid cell modulation strategy represents a promising therapeutic avenue for PDAC, offering hope for improved treatment for this otherwise difficult-to-treat malignancy.

Source: Cell Reports Medicine

DOI: 10.1016/j.xcrm.2026.102938