Knockdown of the interleukin-6 receptor alpha chain of dendritic cell vaccines enhances the therapeutic potential against IL-6 producing tumors.

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.

• Authors: Wonchan Hwang, Keunok Jung, Youkyoung Jeon, Shik Yun, Tae Woo Kim, Inhak Choi
• Journal: Vaccine (Vaccine) Vol. 29 Issue 1 Pg. 34-44 (Dec 10 2010) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 20974308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Cancer Vaccines
• Interleukin-6
• Interleukin-6 Receptor alpha Subunit

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology)
• Dendritic Cells (immunology)
• Female
• Gene Knockdown Techniques
• Interleukin-6 (metabolism)
• Interleukin-6 Receptor alpha Subunit (biosynthesis)
• Mice
• Mice, Inbred C57BL
• Neoplasms (immunology, therapy)
• T-Lymphocytes, Cytotoxic (immunology)