Knockdown of the interleukin-6 receptor alpha chain of dendritic cell vaccines enhances the therapeutic potential against IL-6 producing tumors.
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.
Department of Microbiology and Immunology, Advanced Research Center for Multiple Myeloma, Inje University College of Medicine, 633-165 Gaegum-Dong Jin-Gu, Busan 614-735, Republic of Korea.
Wonchan
W
Hwang
Keunok
K
Jung
Youkyoung
Y
Jeon
Shik
S
Yun
Tae Woo
TW
Kim
Inhak
I
Choi
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D055785:Gene Knockdown Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D053698:Interleukin-6 Receptor alpha Subunit / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019496:Cancer Vaccines; D015850:Interleukin-6; D053698:Interleukin-6 Receptor alpha Subunit