Date of Award

12-2009

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Microbiology

Advisor

Wei, Yanzhang

Committee Member

Scott , Thomas R

Committee Member

Temesvari , Lesly A

Committee Member

Wagner , Thomas E

Abstract

Dendritic cell-mediated cancer immunotherapy employs several ways to engage tumor antigens. We have demonstrated both in pre-clinical animal studies and early clinical trials that dendritomas, highly purified hybrids between dendritic cells and tumor cells, are superior activators of anti-tumor immunity. In the present study, we examined the expression profile of several inflammatory chemokine and chemokine receptors of dendritomas by RNA microarray and real-time RT-PCR. The results indicate that dendritomas made from immature DCs and tumor cells express higher levels of CCL3, CCL5, and CCL22 and lower levels of CCR2 and CCR5, which mimics LPS matured DCs, while dendritomas made from mature DCs and tumor cells show a reversed expression profile of these genes: decreased levels of CCLs and increased levels of CCRs. Our data support the notion that dendritomas made from immature DCs and tumor cells may be more effective in migration from the injection site to draining lymph nodes and therefore make them more effective in stimulating anti-tumor immunity.
Morinda citrifolia (Noni) has been used as a folk remedy to treat a myriad of ailments, and is gaining in popularity as a modern dietary supplement to enhance the immune system. Recent studies have shown that Noni juice has anticancer activity. Studies from our lab demonstrated that fermented Noni juice not only prevents mouse sarcoma tumor development but also eradicates existing tumors. Fermented Noni can also directly engage dendritic cells with B cells. Since Noni contains a wide array of microorganisms, and upon fermentation, all but one are killed, it is presumed to contain a plethora of degraded microbial products that would serve as microbial stress signals. We hypothesized that Noni may activate dendritic cells by engaging their toll-like receptors (TLRs), and investigated genes associated with TLR signaling via real-time RT-PCR. It was determined that Noni stimulates early low levels of inflammatory cytokines, followed by a latent upregulation of anti-inflammatory mediators. Intriguingly, Noni also appeared to trans-differentiate dendritic cells toward macrophage-like cells.

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Microbiology Commons

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