PMID- 21479379
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20121002
LR  - 20130222
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 1
IP  - 1
DP  - 2008 Jan-Feb
TI  - SOCS1 silencing can break high-dose dendritic cell immunotherapy-induced immune 
      tolerance.
PG  - 61-70
AB  - Dendritic cells (DCs) play a pivotal role in T cell-mediated immunity and have 
      been shown to induce strong anti-tumor immune responses. As of yet, only a 
      limited number of objective tumor regressions have been observed in clinical 
      studies using a DC vaccine. Suppressor of cytokine signaling-1 (SOCS1) is a key 
      negative regulator of the JAK/STAT signal pathway and plays an essential role in 
      suppressing systemic autoimmunity that is mediated by DCs. The aim of this study 
      was to investigate whether SOCS1-silenced DCs can break the vaccine-induced 
      immune tolerance stimulated by high-dose DC, thereby enhancing anti-tumor 
      activity. In the mouse melanoma model, we found that a 2x106 TRP2-pulsed DC 
      vaccine was able to induce immune tolerance, while a 2x106 SOCS1-silenced DC/TRP2 
      vaccine prevented immune tolerance. Further experiments revealed that 
      activation-induced T cell death (AICD) through the Fas/Fas-L pathway may play a 
      crucial role in immune tolerance induced by 2x106 TRP2-pulsed DC. SOCS1-silencing 
      in DCs could prevent immune tolerance by inhibiting Fas and Fas-L expression, 
      induced by an increase in IL-12p70 and IL-6 production. In addition, in 2x106 
      SOCS1-silenced DC/TRP2 immunized mice, higher levels of IL-12p70 and IFN-gamma and 
      lower IL-17 production may inhibit tumor angiogenesis and therefore assist in 
      breaking immune tolerance. In conclusion, high-doses of DCs can inhibit the 
      vaccine-induced AICD of T cells and cytokine regulation in tumor angiogenesis. 
      These results indicate that SOCS1-silenced DC vaccines may greatly enhance 
      anti-tumor activity by breaking self-tolerance.
FAU - Hu, Qinghai
AU  - Hu Q
AD  - Shanghai Jiao Tong University Medical School, Shanghai Institute of Immunology, 
      Shanghai 200025, P.R. China.
FAU - Qin, Xia
AU  - Qin X
FAU - Qian, Gaochao
AU  - Qian G
FAU - Jiang, Shan
AU  - Jiang S
FAU - Li, Haiyan
AU  - Li H
FAU - Jiang, Min
AU  - Jiang M
FAU - Li, Xiaoyan
AU  - Li X
FAU - Chen, Si-Yi
AU  - Chen SY
FAU - Zang, Ying Qin
AU  - Zang YQ
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
EDAT- 2008/01/01 00:00
MHDA- 2008/01/01 00:01
CRDT- 2011/04/12 06:00
PHST- 2011/04/12 06:00 [entrez]
PHST- 2008/01/01 00:00 [pubmed]
PHST- 2008/01/01 00:01 [medline]
PST - ppublish
SO  - Mol Med Rep. 2008 Jan-Feb;1(1):61-70.