Cell-specific nanoengineering strategy to disrupt tolerogenic signaling from myeloid-derived suppressor cells and invigorate antitumor immunity in pancreatic cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is characterized by intratumoral abundance of neutrophilic/polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) which exert anti-T-cell functions through multiple mechanisms, especially JAK2/STAT3-regulated arginase activity. To overcome limitations of systemic inhibition of PMN-MDSCs in cancer-bearing patients such as neutropenia and compensatory myelopoietic adaptations, we developed a nanoengineering strategy to disrupt cell-specific signaling exclusively in PMN-MDSCs without compromising viability or provoking neutropenia. Single-cell RNA sequencing in human/murine PDAC, and flow cytometry in peripheral blood cells from treatment-naïve PDAC patients, nominated surface receptor CXCR2 as a PMN-MDSC-exclusive target. We chemically modified

SUBMITTER: Deshpande NU 

PROVIDER: S-EPMC12185796 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature