PMID- 30524902
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210112
IS  - 2162-4011 (Print)
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Linking)
VI  - 7
IP  - 12
DP  - 2018
TI  - Dendritic cell-based vaccination: powerful resources of immature dendritic cells 
      against pancreatic adenocarcinoma.
PG  - e1504727
LID - 10.1080/2162402X.2018.1504727 [doi]
LID - e1504727
AB  - Pancreatic adenocarcinoma (PAC) has a poor prognosis. One treatment approach, 
      investigated here, is to reinforce antitumor immunity. Dendritic cells (DCs) are 
      essential for the development and regulation of adaptive host immune responses 
      against tumors. A major role for DCs may be as innate tumoricidal effector cells. 
      We explored the efficacy of vaccination with immature (i)DCs, after selecting 
      optimal conditions for generating immunostimulatory iDCs. We used two models, 
      C57BL/6Jrj mice with ectopic tumors induced by the PAC cell line, Panc02, and 
      genetically engineered (KIC) mice developing PAC. Therapeutic iDC-vaccination 
      resulted in a significant reduction in tumor growth in C57BL/6Jrj mice and 
      prolonged survival in KIC mice. Prophylactic iDC-vaccination prevented 
      subcutaneous tumor development. These protective effects were long-lasting in 
      Panc02-induced tumor development, but not in melanoma. iDC-vaccination impacted 
      the immune status of the hosts by greatly increasing the percentage of CD8(+) 
      T-cells, and natural killer (NK)1.1(+) cells, that express granzyme B associated 
      with Lamp-1 and IFN-gamma. Efficacy of iDC-vaccination was CD8(+) T-cell-dependent 
      but NK1.1(+) cell-independent. We demonstrated the ability of DCs to produce 
      peroxynitrites and to kill tumor cells; this killing activity involved 
      peroxynitrites. Altogether, these findings make killer DCs the pivotal actors in 
      the beneficial clinical outcome that accompanies antitumor immune responses. We 
      asked whether efficacy can be improved by combining DC-vaccination with the 
      FOLFIRINOX regimen. Combined treatment significantly increased the lifespan of 
      KIC mice with PAC. Prolonged treatment with FOLFIRINOX clearly augmented this 
      beneficial effect. Combining iDC-vaccination with FOLFIRINOX may therefore 
      represent a promising therapeutic option for patients with PAC.
FAU - Collignon, Aurelie
AU  - Collignon A
AUID- ORCID: 0000-0002-0562-5646
AD  - Aix Marseille Univ, INSERM, CRO2, Centre de Recherche en Oncologie biologique et 
      Oncopharmacologie, Marseille, France.
FAU - Silvy, Francoise
AU  - Silvy F
AUID- ORCID: 0000-0002-0562-5646
AD  - Aix Marseille Univ, INSERM, CRO2, Centre de Recherche en Oncologie biologique et 
      Oncopharmacologie, Marseille, France.
FAU - Robert, Stephane
AU  - Robert S
AUID- ORCID: 0000-0001-9426-0775
AD  - Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France.
FAU - Trad, Malika
AU  - Trad M
AUID- ORCID: 0000-0001-9085-8518
AD  - CHU Dijon-Bocage, Medecine interne et Immunologie Clinique, Dijon, France.
FAU - Germain, Sebastien
AU  - Germain S
AUID- ORCID: 0000-0002-8744-9489
AD  - Aix Marseille Univ, INSERM, CRO2, Centre de Recherche en Oncologie biologique et 
      Oncopharmacologie, Marseille, France.
FAU - Nigri, Jeremy
AU  - Nigri J
AUID- ORCID: 0000-0003-1439-391X
AD  - Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Cancer Research 
      Center of Marseille, Marseille, France.
FAU - Andre, Frederic
AU  - Andre F
AUID- ORCID: 0000-0002-6298-395X
AD  - Aix Marseille Univ, INSERM, CRO2, Centre de Recherche en Oncologie biologique et 
      Oncopharmacologie, Marseille, France.
FAU - Rigot, Veronique
AU  - Rigot V
AUID- ORCID: 0000-0003-1358-1863
AD  - Aix Marseille Univ, INSERM, CRO2, Centre de Recherche en Oncologie biologique et 
      Oncopharmacologie, Marseille, France.
FAU - Tomasini, Richard
AU  - Tomasini R
AUID- ORCID: 0000-0003-0869-0811
AD  - Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Cancer Research 
      Center of Marseille, Marseille, France.
FAU - Bonnotte, Bernard
AU  - Bonnotte B
AUID- ORCID: 0000-0002-1098-4598
AD  - CHU Dijon-Bocage, Medecine interne et Immunologie Clinique, Dijon, France.
FAU - Lombardo, Dominique
AU  - Lombardo D
AUID- ORCID: 0000-0001-5877-7013
AD  - Aix Marseille Univ, INSERM, CRO2, Centre de Recherche en Oncologie biologique et 
      Oncopharmacologie, Marseille, France.
FAU - Mas, Eric
AU  - Mas E
AUID- ORCID: 0000-0002-8925-9195
AD  - Aix Marseille Univ, INSERM, CRO2, Centre de Recherche en Oncologie biologique et 
      Oncopharmacologie, Marseille, France.
FAU - Beraud, Evelyne
AU  - Beraud E
AUID- ORCID: 0000-0002-1098-4598
AD  - Aix Marseille Univ, INSERM, CRO2, Centre de Recherche en Oncologie biologique et 
      Oncopharmacologie, Marseille, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180925
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
PMC - PMC6279335
OTO - NOTNLM
OT  - Active immunotherapy
OT  - DC-based tumor immunotherapy
OT  - FOLFIRINOX
OT  - animal models
OT  - cancer vaccines
OT  - pancreatic cancer
EDAT- 2018/12/14 06:00
MHDA- 2018/12/14 06:01
PMCR- 2019/09/25
CRDT- 2018/12/08 06:00
PHST- 2018/01/25 00:00 [received]
PHST- 2018/07/19 00:00 [revised]
PHST- 2018/07/21 00:00 [accepted]
PHST- 2018/12/08 06:00 [entrez]
PHST- 2018/12/14 06:00 [pubmed]
PHST- 2018/12/14 06:01 [medline]
PHST- 2019/09/25 00:00 [pmc-release]
AID - 1504727 [pii]
AID - 10.1080/2162402X.2018.1504727 [doi]
PST - epublish
SO  - Oncoimmunology. 2018 Sep 25;7(12):e1504727. doi: 10.1080/2162402X.2018.1504727. 
      eCollection 2018.