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-6R alpha) 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-6R alpha knockdown-DC vaccine significantly enhanced the frequency of tumor-specific CD8(+) CTLs-producing effector molecules such as IFN-gamma, TNF-alpha, FasL, perforin, and granzyme B, and generated more CD8(+) memory T cells, leading to the substantially prolonged survival of TC-1 tumor-bearing mice. (C) 2010 Elsevier Ltd. All rights reserved.