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• W2968831388 abstract "Background. Cancer vaccines have largely failed to induce clinically-meaningful responses in breast cancer. Part of the issue is that the microenvironment at the site of tumors is inadequate and cannot efficiently attract T cells and other effectors, or create an appropriate microenvironment favoring the destruction of tumor. In this study we investigate the development of innate immune effector DC activated with toll like receptor agonists. Methods. In this study, human monocyte-derived DC were activated with either IFN-#947;/LPS or IL-1#946;, IL-6, TNF-#945; and PGE2 (CM DC). For INF-#947;/LPS activated DC the cells were harvested at either 6 hour (early) or 24 hour (mature) after LPS treatment. Breast cancer cells were labeled with CFSE and co-cultured with DCs for 18 hours, then stained with 7-AAD and subjected by flow cytometric analysis. DC derived cytokines and chemokines were measured by ELISA and intracellular TNF-related apoptosis inducing ligand (TRAIL) was detected by flow cytometry. Results. The results demonstrated that DC activated with IFN-#947; /LPS unlike CM DC produce abundant levels of IL-12, and TNF-#945;, chemokines IP-10, MIP-1#945;, MIP-1#946;, and RANTES. These DC compared with iDC and CM DC also demonstrated a significant capacity to lyse breast cancer cell lines. Interestingly early (6-hour) IFN-#947;/LPS treated DC demonstrated a substantially greater cytotoxicity against tumor cells than late mature (24-hour) IFN-#947;/LPS DC. At least part of the lytic activity was due to soluble TNF-#945; not requiring cell contact and inhibited by anti-TNF-#945;. IFN-#947;/LPS activated DC unlike CM DC also expressed high levels of TRAIL in greater quantities early following activation suggesting the remaining lytic activity may be mediated by TRAIL. There was no evidence of perforin or granzyme expression in the DC. Early IFN-#947;/LPS DC exhibited enhanced ability to uptake antigen compared with late mature DC. Conclusions. Our results indicate that TLR/IFN-#947; activated DC unlike CM DC are endowed with multiple effector functions, including high level cytokine production (i.e. IL-12), chemokine production to attract lymphocytes and NK cells , direct tumoricidal activity mediated by TNF family members, and potent antigen specific T cell stimulating capacity mediated by IL-12. Peritumoral injection of these DC may condition the immune response locally at the tumor site to improve the efficacy of cancer immunotherapy. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4148." @default.
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• W2968831388 date "2009-05-01" @default.
• W2968831388 modified "2023-09-26" @default.
• W2968831388 title "Abstract #4148: Developing activated innate immune effectors using toll-like receptor agonist activated dendritic cells (DC) to condition the local immune response in the breast" @default.
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