PMID- 17473921 OWN - NLM STAT- MEDLINE DCOM- 20071025 LR - 20240426 IS - 0340-7004 (Print) IS - 1432-0851 (Electronic) IS - 0340-7004 (Linking) VI - 56 IP - 11 DP - 2007 Nov TI - TGF-beta insensitive dendritic cells: an efficient vaccine for murine prostate cancer. PG - 1785-93 AB - Dendritic cells (DCs) are highly potent initiators of the immune response, but DC effector functions are often inhibited by immunosuppressants such as transforming growth factor beta (TGF-beta). The present study was conducted to develop a treatment strategy for prostate cancer using a TGF-beta-insensitive DC vaccine. Tumor lysate-pulsed DCs were rendered TGF-beta insensitive by dominant-negative TGF-beta type II receptor (TbetaRIIDN), leading to the blockade of TGF-beta signals to members of the Smad family, which are the principal cytoplasmic intermediates involved in the transduction of signals from TGF-beta receptors to the nucleus. Expression of TbetaRIIDN did not affect the phenotype of transduced DCs. Phosphorylated Smad-2 was undetectable and expression of surface co-stimulatory molecules (CD80/CD86) were upregulated in TbetaRIIDN DCs after antigen and TGF-beta1 stimulation. Vaccination of C57BL/6 tumor-bearing mice with the TbetaRIIDN DC vaccine induced potent tumor-specific cytotoxic T lymphocyte responses against TRAMP-C2 tumors, increased serum IFN-gamma and IL-12 level, inhibited tumor growth and increased mouse survival. Furthermore, complete tumor regression occurred in two vaccinated mice. These results demonstrate that blocking TGF-beta signals in DC enhances the efficacy of DC-based vaccines. FAU - Wang, Fu-Li AU - Wang FL AD - Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. FAU - Qin, Wei-Jun AU - Qin WJ FAU - Wen, Wei-Hong AU - Wen WH FAU - Tian, Feng AU - Tian F FAU - Song, Bin AU - Song B FAU - Zhang, Qiang AU - Zhang Q FAU - Lee, Chung AU - Lee C FAU - Zhong, Wei-de AU - Zhong WD FAU - Guo, Ying-Lu AU - Guo YL FAU - Wang, He AU - Wang H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070501 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Antineoplastic Agents) RN - 0 (Cancer Vaccines) RN - 0 (Receptors, Transforming Growth Factor beta) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II) SB - IM MH - Animals MH - Antineoplastic Agents/*pharmacology MH - *Cancer Vaccines/therapeutic use MH - Cell Line, Tumor MH - Dendritic Cells/immunology/*transplantation MH - Immunotherapy MH - Lymphocyte Activation/drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Prostatic Neoplasms/*drug therapy MH - *Protein Serine-Threonine Kinases/genetics/metabolism MH - Receptor, Transforming Growth Factor-beta Type II MH - *Receptors, Transforming Growth Factor beta/genetics/metabolism MH - Signal Transduction MH - T-Lymphocytes/drug effects/immunology PMC - PMC11030160 EDAT- 2007/05/03 09:00 MHDA- 2007/10/27 09:00 PMCR- 2007/05/01 CRDT- 2007/05/03 09:00 PHST- 2006/11/19 00:00 [received] PHST- 2007/03/23 00:00 [accepted] PHST- 2007/05/03 09:00 [pubmed] PHST- 2007/10/27 09:00 [medline] PHST- 2007/05/03 09:00 [entrez] PHST- 2007/05/01 00:00 [pmc-release] AID - 322 [pii] AID - 10.1007/s00262-007-0322-3 [doi] PST - ppublish SO - Cancer Immunol Immunother. 2007 Nov;56(11):1785-93. doi: 10.1007/s00262-007-0322-3. Epub 2007 May 1.