scholarly journals CD40ligand‐expressing dendritic cells induce regression of hepatocellular carcinoma by activating innate and acquired immunity in vivo

Hepatology ◽  
2008 ◽  
Vol 48 (1) ◽  
pp. 157-168 ◽  
Author(s):  
Maria A. Gonzalez‐Carmona ◽  
Veronika Lukacs‐Kornek ◽  
Anne Timmerman ◽  
Sara Shabani ◽  
Miroslaw Kornek ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3375
Author(s):  
Annabelle Vogt ◽  
Farsaneh Sadeghlar ◽  
Tiyasha H. Ayub ◽  
Carlo Schneider ◽  
Christian Möhring ◽  
...  

Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the maturation of DC and T-cell priming. In this study, the impact of intratumoral (i.t.) CD40L-expressing DC to improve vaccination with murine (m)AFP-transduced DC (Ad-mAFP-DC) was analyzed in subcutaneous (s.c.) and orthotopic murine HCC. Murine DC were adenovirally transduced with Ad-mAFP or Ad-CD40L. Hepa129-mAFP-cells were injected into the right flank or the liver of C3H-mice to induce subcutaneous (s.c.) and orthotopic HCC. For treatments, 106 Ad-mAFP-transduced DC were inoculated s.c. followed by 106 CD40L-expressing DC injected intratumorally (i.t.). S.c. inoculation with Ad-mAFP-transduced DC, as vaccine, induced a delay of tumor-growth of AFP-positive HCC compared to controls. When s.c.-inoculation of Ad-mAFP-DC was combined with i.t.-application of Ad-CD40L-DC synergistic antitumoral effects were observed and complete remissions and long-term survival in 62% of tumor-bearing animals were achieved. Analysis of the tumor environment at different time points revealed that s.c.-vaccination with Ad-mAFP-DC seems to stimulate tumor-specific effector cells, allowing an earlier recruitment of effector T-cells and a Th1 shift within the tumors. After i.t. co-stimulation with Ad-CD40L-DC, production of Th1-cytokines was strongly increased and accompanied by a robust tumor infiltration of mature DC, activated CD4+-, CD8+-T-cells as well as reduction of regulatory T-cells. Moreover, Ad-CD40L-DC induced tumor cell apoptosis. Intratumoral co-stimulation with CD40L-expressing DC significantly improves vaccination with Ad-mAFP-DC in pre-established HCC in vivo. Combined therapy caused an early and strong Th1-shift in the tumor environment as well as higher tumor apoptosis, leading to synergistic tumor regression of HCC. Thus, CD40L co-stimulation represents a promising tool for improving DC-based immunotherapy of HCC.


2018 ◽  
Vol 18 (4) ◽  
pp. 535-546 ◽  
Author(s):  
Nahla E. El-Ashmawy ◽  
Enas A. El-Zamarany ◽  
Eman G. Khedr ◽  
Hoda A. El-Bahrawy ◽  
Ola A. El-Feky

2003 ◽  
Vol 11 (4) ◽  
pp. 408-410
Author(s):  
Jian-Wei Guo ◽  
Li-Wei Qin ◽  
Mei-Ying Cai ◽  
Tong-De Lu

2013 ◽  
Vol 34 (3) ◽  
pp. 447-461 ◽  
Author(s):  
Annabelle Vogt ◽  
Elisabeth Sievers ◽  
Veronika Lukacs-Kornek ◽  
Georges Decker ◽  
Esther Raskopf ◽  
...  

2002 ◽  
Vol 168 (3) ◽  
pp. 1294-1301 ◽  
Author(s):  
Xinan Jiao ◽  
Richard Lo-Man ◽  
Pierre Guermonprez ◽  
Laurence Fiette ◽  
Edith Dériaud ◽  
...  

2011 ◽  
Vol 54 ◽  
pp. S91
Author(s):  
M.A. Gonzalez-Carmona ◽  
A. Vogt ◽  
T.H. Ayub ◽  
G. Decker ◽  
Y. Yildiz ◽  
...  

2010 ◽  
Vol 34 (8) ◽  
pp. S72-S72
Author(s):  
Qi Xu ◽  
Xiumin Ma ◽  
Yuejie Zhu ◽  
Fengsen Li ◽  
Jianbing Ding

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