PMID- 18537185
OWN - NLM
STAT- MEDLINE
DCOM- 20080826
LR  - 20220321
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 48
IP  - 1
DP  - 2008 Jul
TI  - CD40ligand-expressing dendritic cells induce regression of hepatocellular 
      carcinoma by activating innate and acquired immunity in vivo.
PG  - 157-68
LID - 10.1002/hep.22296 [doi]
AB  - Dendritic cells (DCs) are professional antigen-presenting cells able to prime 
      T-cells against tumor-associated antigens (TAA), but their potential to induce 
      hepatocellular carcinoma (HCC) regression is still limited. CD40/CD40L 
      interaction is essential for DC activation and induction of antigen-specific 
      T-cells. In this study, transduction of TAA-pulsed DC with a CD40L-encoding 
      adenovirus (Ad-CD40L) was used to improve the immune response induced by DC 
      toward HCC. Bone marrow-derived DC from C3H/HeNcrl mice were cultured with 
      granulocyte-macrophage colony-stimulating factor and interleukin-4. On day 6, 
      tumor-lysate pulsed DCs were infected with adenoviruses. HCCs were induced by 
      inoculation of mice with Hepa129-cells subcutaneously. When tumor-volume was 100 
      to 400 mm(3), DCs were injected intratumorally, subcutaneously, or intravenously. 
      Ad-CD40L transduction exerted CD40/CD40L interactions between DCs, increasing DC 
      immunostimulation with up-regulation of CD80/CD86- and interleukin-12 (IL-12) 
      expression. Intratumoral injection of CD40L-DC was superior to intravenous or 
      subcutaneous treatments, yielding tumor elimination in almost 70% of mice. 
      Moreover, all tumor-free animals were protected against hepatic tumor cell 
      rechallenge. In a preventive setting, subcutaneous injection of CD40L-expressing 
      DCs protected 50% of mice for more than 3 months toward tumor cell challenge. The 
      induced immune response seemed to be dependent on cross-priming with 
      Th1-lymphocytes in the lymph nodes, because transduced DCs were redetected in 
      lymphoid tissues. In addition, immunohistochemistry of tumors indicated a 
      significant tumor infiltration with CD4+, CD8+ T cells and natural killer (NK) 
      cells. Tumor-infiltrating lymphocytes were tumor-specific, as shown in 
      interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot and T-cell 
      proliferation assays. CONCLUSION: Transduction of DCs with Ad-CD40L increases 
      significantly the stimulatory capacity of DCs. Intratumoral injection of DCs 
      activates both acquired and innate immunity, inducing complete regression of 
      established tumors and long-term immunity against tumor recurrence. This approach 
      improves the antitumoral potential of DCs.
FAU - Gonzalez-Carmona, Maria A
AU  - Gonzalez-Carmona MA
AD  - Department of Internal Medicine I, University of Bonn, Bonn, Germany.
FAU - Lukacs-Kornek, Veronika
AU  - Lukacs-Kornek V
FAU - Timmerman, Anne
AU  - Timmerman A
FAU - Shabani, Sara
AU  - Shabani S
FAU - Kornek, Miroslaw
AU  - Kornek M
FAU - Vogt, Annabelle
AU  - Vogt A
FAU - Yildiz, Yildiz
AU  - Yildiz Y
FAU - Sievers, Elisabeth
AU  - Sievers E
FAU - Schmidt-Wolf, Ingo G H
AU  - Schmidt-Wolf IG
FAU - Caselmann, Wolfgang H
AU  - Caselmann WH
FAU - Sauerbruch, Tilman
AU  - Sauerbruch T
FAU - Schmitz, Volker
AU  - Schmitz V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 147205-72-9 (CD40 Ligand)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - CD40 Ligand/*metabolism
MH  - Carcinoma, Hepatocellular/*immunology/pathology/surgery
MH  - Cell Line, Tumor
MH  - Coculture Techniques
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/*immunology/metabolism/*transplantation
MH  - Disease Progression
MH  - Immunity, Active
MH  - Immunity, Innate
MH  - Injections, Intralesional
MH  - Interleukin-12/blood/metabolism
MH  - Liver Neoplasms, Experimental/*immunology/pathology/surgery
MH  - Lymphocytes/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Neoplasm Recurrence, Local/prevention & control
MH  - Phenotype
MH  - Spleen/cytology
MH  - Transduction, Genetic
MH  - Vaccination
EDAT- 2008/06/10 09:00
MHDA- 2008/08/30 09:00
CRDT- 2008/06/10 09:00
PHST- 2008/06/10 09:00 [pubmed]
PHST- 2008/08/30 09:00 [medline]
PHST- 2008/06/10 09:00 [entrez]
AID - 10.1002/hep.22296 [doi]
PST - ppublish
SO  - Hepatology. 2008 Jul;48(1):157-68. doi: 10.1002/hep.22296.