Pancreatic cancer-derived exosomes induce apoptosis of T lymphocytes through the p38 MAPK signal transduction pathway

Pancreatic cancer is the fourth most lethal malignancy, which is characterized by poor immunogenicity. Pancreatic cancer cells take various strategies to suppress host immune response, evade immune defenses, and facilitate tumor growth and development. As a mode of long-range intercellular communication, cancer-derived exosomes contribute to the impairment of the immune system. However, the mechanisms that induce changes in the activities of signal transduction pathways in immune cells, which are influenced by tumor-derived exosomes, are poorly understood. We treated peripheral T lymphocytes with pancreatic cancer-derived exosomes, performed RNA-seq and Gene Set Enrichment Analysis to explore the pivotal signaling pathway that mediates apoptosis in exosomes-treated T lymphocytes. T lymphoblasts were obtained from three donors and total RNA was isolated from cells with exosomes treated (Exo-T) or with PBS treated (Ctrl-T).