Abstract
AB059. Mutant KRAS cells release tumor specific exosomes that create an immunosuppressive phenotype in lung tumor microenvironment
Savvas Petanidis1, Kalliopi Domvri2, Zogas Nikolaos3, Paul Zarogoulidis2, Efrosini Kioseoglou1, Doxakis Anestakis4,5, Konstantinos Zarogoulidis2, Athanasios Salifoglou1
1Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, Greece;2Pulmonary Department-Oncology Unit, General Hospital “G. Papanikolaou”, Aristotle University of Thessaloniki, Thessaloniki, Greece;3Gene and Cell Therapy Center, Hematology Department-Bone Marrow Transplantation Unit, George Papanicolaou Hospital, Thessaloniki, Greece;4Department of Medicine, Laboratory of General Biology, 5Department of Medicine, Laboratory of Forensic Medicine and Toxicology, Aristotle University of Thessaloniki, Thessaloniki, Greece
Background: To investigate whether KRAS-secreted exosomal RNAs contribute to metastatic related-EMT phenotype, and their association with the hypoxic immunosuppressive phenotype in lung carcinoma.
Methods: Lung cancer patient tissues and mice were used for exosome isolation. Exosomal molecular characterization was performed using Immunofluorescence microscopy, microRNA analysis and immunohistochemistry.
Results: The findings reveal that mutant KRAS secreted exosomes contain high expression of oncogenic miR-31/miR-182/miR-205 which are associated with HIF-2a-related hypoxia. Furthermore, exosomal secretion in lung tumor microenvironment caused accumulation of IL-10, CTL-4 and IDO suggesting KRAS-dependent exosomal immunosuppression that drives EMT-related lung metastasis.
Conclusions: These findings suggest that KRAS secreted exosomal miRNAs can modulate the hypoxic immunosuppressive mechanism in lung tumor microenvironment and trigger the EMT-related metastatic niche.
Keywords: Lung cancer; KRAS; hypoxia; immunosuppression
doi: 10.21037/atm.2016.AB059
Cite this abstract as: Petanidis S, Domvri K, Nikolaos Z, Zarogoulidis P, Kioseoglou E, Anestakis D, Zarogoulidis K, Salifoglou A. Mutant KRAS cells release tumor specific exosomes that create an immunosuppressive phenotype in lung tumor microenvironment. Ann Transl Med 2016;4(22):AB059. doi: 10.21037/atm.2016.AB059
