Single-cell analysis reveals nanosecond pulsed electric field ablation induced myeloid cells remodeling in pancreatic cancer

Abstract

Nanosecond pulsed electric field (nsPEF) treatment has emerged as a promising and effective approach for pancreatic cancer. Tumor-infiltrating myeloid cells are crucial tumor regulators and potential immunotherapy targets. Understanding the effect of nsPEF on the myeloid cells in tumors is necessary for grasping the anti-tumor impact of nsPEF therapy. This study describes the phenotype and function of myeloid cells in Panc02 pancreatic cancer mouse models on day three after nsPEF using single-cell RNA sequencing (scRNA-Seq). Defining comparable myeloid cells in Panc02 tumors enabled characterization of their response to nsPEF treatment. Treatment with nsPEF increased infiltration by monocytes/macrophages, which participated in forming a immunosuppressive tumor microenvironment. NsPEF also promoted the recruitment of dendritic cells to tumors. Our comprehensive investigation of crucial myeloid subsets and significant cellular interactions regulating tumor immunity indicated that the nsPEF induced a compartmental remodeling of tumor-infiltrating myeloid cells in pancreatic cancer. These results provide information for interpreting the complex immune changes after nsPEF treatment in pancreatic cancer and may guide future therapeutic interventions.

Keywords: Myeloid cells; Nanosecond pulsed electric field; Pancreatic cancer; Single-cell RNA sequencing; Tumor ablation.