The tautomerase activity of tumor exosomal MIF is crucial to promoting pancreatic cancer progression via modulating MDSC differentiation

Pancreatic cancer represents a devastating disease and is the third most prevalent cause of cancer-related mortality. Substantial evidence suggests that tumor-derived exosomes contribute to the immunosuppressive activity mediated by myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME). However, the precise underlying mechanisms remain elusive. This study presents evidence demonstrating that exosomes derived from human or murine pancreatic cancer induce the differentiation of human CD14+ monocytes or mouse bone marrow cells into MDSCs. We further identified macrophage migration inhibitory factor (MIF) as a significant component of both human and murine pancreatic cancer-derived exosomes. Upon specific knockdown of MIF using an shRNA approach, the ability of pancreatic cancer-derived exosomes to promote MDSC formation was abrogated.