Efficacy of vaccination with tumor-exosome loaded dendritic cells combined with cytotoxic drug treatment in pancreatic cancer

• Verfasst von: Xiao, Li [VerfasserIn]
• Verfasst von: Erb, Ulrike [VerfasserIn]
• Verfasst von: Zhao, Kun [VerfasserIn]
• Verfasst von: Hackert, Thilo [VerfasserIn]
• Verfasst von: Zöller, Margot [VerfasserIn]
• Titel: Efficacy of vaccination with tumor-exosome loaded dendritic cells combined with cytotoxic drug treatment in pancreatic cancer
• Verf.angabe: Li Xiao, Ulrike Erb, Kun Zhao, Thilo Hackert & Margot Zöller
• E-Jahr: 2017
• Jahr: 30 May 2017
• Umfang: 16 S.
• Teil: volume:6
• Teil: year:2017
• Teil: number:6
• Teil: elocationid:e1319044
• Teil: extent:16
• Fussnoten: Gesehen am 22.10.2018
• Titel Quelle: Enthalten in: OncoImmunology
• Ort Quelle: Abingdon : Taylor & Franics, 2012
• Jahr Quelle: 2017
• Band/Heft Quelle: 6(2017), 6, Artikel-ID e1319044
• ISSN Quelle: 2162-402X
• DOI: doi:10.1080/2162402X.2017.1319044
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cytotoxic drugs
• Sach-SW: dendritic cell vaccination
• Sach-SW: myeloid-derived suppressor cells
• Sach-SW: pancreatic cancer
• Sach-SW: tumor exosomes
• K10plus-PPN: 1582152578

Abstract

Pancreatic cancer (PaCa) has a dismal prognosis and adjuvant immunotherapy frequently is of low efficacy due to immunosuppressive features of PaCa and PaCa-stroma. We here explored, whether the efficacy of vaccination with tumor-exosome (TEX)-loaded dendritic cells (DC) can be improved by combining with drugs affecting myeloid-derived suppressor cells (MDSC). Experiments were performed with the UNKC6141 PaCa line. UNKC6141 TEX-loaded DC were weekly intravenously injected, mice additionally receiving Gemcitabine (GEM) and/or ATRA and/or Sunitinib (Sun). UNKC6141 grow aggressively after subcutaneous and orthotopic application and are consistently recovered in peripheral blood, bone marrow, lung and frequently liver. Vaccination with DC-TEX significantly prolonged the survival time, the efficacy of DC-TEX exceeding that of the cytotoxic drugs. However, ATRA, Sun and most efficiently GEM, sufficed for a pronounced reduction of MDSC including tumor-infiltrating MDSC, which was accompanied by a decrease in migrating and metastasizing tumor cells. When combined with DC-TEX vaccination, a higher number of activated T cells was recovered in the tumor and the survival time was prolonged compared with only DC-TEX vaccinated mice. As ATRA, GEM and Sun affect MDSC at distinct maturation and activation stages, a stronger support for DC-TEX vaccination was expected by the drug combination. Intrapancreatic tumor growth was prevented beyond the death of control mice. However, tumors developed after a partial breakdown of the immune system by the persisting drug application. Nonetheless, in combination with optimized drug tuning to prevent MDSC maturation and activation, vaccination with TEX-loaded DC appears a most promising option in PaCa therapy.