TY - JOUR
T1 - Knockdown of the interleukin-6 receptor alpha chain of dendritic cell vaccines enhances the therapeutic potential against IL-6 producing tumors
AU - Hwang, Wonchan
AU - Jung, Keunok
AU - Jeon, Youkyoung
AU - Yun, Shik
AU - Kim, Tae Woo
AU - Choi, Inhak
N1 - Funding Information:
This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea ( 0620310 and 0920040 for I. Choi).
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2010/12/10
Y1 - 2010/12/10
N2 - Tumor microenvironment has emerged as one of the major obstacles against the clinical efficacy of dendritic cell (DC) vaccines. Tumor-derived IL-6 may inhibit the differentiation of hematopoietic progenitor cells into DCs and suppress DC maturation, rendering DCs tolerogenic. We hypothesized that silencing the IL-6 receptor alpha chain (IL-6Rα) would restore the functional competence of DC vaccines in mice with an IL-6-producing TC-1 tumor, and eventually give rise to protective immunity. We found that the IL-6Rα knockdown-DC vaccine significantly enhanced the frequency of tumor-specific CD8+ CTLs-producing effector molecules such as IFN-γ, TNF-α, FasL, perforin, and granzyme B, and generated more CD8+ memory T cells, leading to the substantially prolonged survival of TC-1 tumor-bearing mice.
AB - Tumor microenvironment has emerged as one of the major obstacles against the clinical efficacy of dendritic cell (DC) vaccines. Tumor-derived IL-6 may inhibit the differentiation of hematopoietic progenitor cells into DCs and suppress DC maturation, rendering DCs tolerogenic. We hypothesized that silencing the IL-6 receptor alpha chain (IL-6Rα) would restore the functional competence of DC vaccines in mice with an IL-6-producing TC-1 tumor, and eventually give rise to protective immunity. We found that the IL-6Rα knockdown-DC vaccine significantly enhanced the frequency of tumor-specific CD8+ CTLs-producing effector molecules such as IFN-γ, TNF-α, FasL, perforin, and granzyme B, and generated more CD8+ memory T cells, leading to the substantially prolonged survival of TC-1 tumor-bearing mice.
KW - Dendritic cell vaccine
KW - IL-6 receptor
KW - Knockdown
UR - http://www.scopus.com/inward/record.url?scp=78649688852&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649688852&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2010.10.027
DO - 10.1016/j.vaccine.2010.10.027
M3 - Article
C2 - 20974308
AN - SCOPUS:78649688852
VL - 29
SP - 34
EP - 44
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 1
ER -
