Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 34-44 |
| Number of pages | 11 |
| Journal | Vaccine |
| Volume | 29 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2010 Dec 10 |
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Keywords
- Dendritic cell vaccine
- IL-6 receptor
- Knockdown
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Infectious Diseases
- Public Health, Environmental and Occupational Health
- veterinary(all)
- Molecular Medicine
Cite this
Knockdown of the interleukin-6 receptor alpha chain of dendritic cell vaccines enhances the therapeutic potential against IL-6 producing tumors. / Hwang, Wonchan; Jung, Keunok; Jeon, Youkyoung; Yun, Shik; Kim, Tae Woo; Choi, Inhak.
In: Vaccine, Vol. 29, No. 1, 10.12.2010, p. 34-44.Research output: Contribution to journal › Article
}
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
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
VL - 29
SP - 34
EP - 44
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 1
ER -