Send to

Choose Destination
Oncoimmunology. 2017 Apr 20;6(6):e1319044. doi: 10.1080/2162402X.2017.1319044. eCollection 2017.

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

Author information

Tumor Cell Biology, University Hospital of Surgery, Heidelberg, Germany.
Section Pancreas Research, University Hospital of Surgery, Heidelberg, Germany.


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.


Cytotoxic drugs; dendritic cell vaccination; myeloid-derived suppressor cells; pancreatic cancer; tumor exosomes

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center