SpecificDioscoreaPhytoextracts Enhance Potency of TCL-Loaded DC-Based Cancer Vaccines

Abstract

Dioscorea tuber phytoextracts can confer immunomodulatory activities ex vivo and improve regeneration of bone marrow cells in vivo. In present study, we evaluated specific Dioscorea phytoextracts for use ex vivo as a bone-marrow-derived dendritic cell- (DC-) based vaccine adjuvant for cancer immunotherapy. Fractionated Dioscorea extracts (DsII) were assayed for their effect on maturation and functions of DC ex vivo and antimelanoma activity of DC-based vaccine in vivo. The phytoextract from 50–75% ethanol-precipitated fraction of Dioscorea alata var. purpurea Tainung no. 5 tuber, designated as DsII-TN5, showed a strong augmentation of tumor cell lysate- (TCL-) loaded DC-mediated activation of T-cell proliferation. DsII-TN5 stimulated the expression of CD40, CD80, CD86, and IL-1β in TCL-loaded DCs and downregulated the expression of TGF-β1. DC vaccines prepared by a specific schema (TCL (2 h) + LPS (22 h)) showed the strongest antitumor activity. DsII-TN5 as a DC vaccine adjuvant showed strong antimelanoma activity and reduced myeloid-derived suppressor cell (MDSC) population in tested mice. DsII-TN5 can also activate DCs to enhance Th1- and Th17-related cytokine expressions. Biochemical analysis showed that DsII-TN5 consists mainly of polysaccharides containing a high level (53%) of mannose residues. We suggest that DsII-TN5 may have potential for future application as a potent, cost-effective adjuvant for DC-based cancer vaccines.

Pleurotus ferulae water extract enhances the maturation and function of murine bone marrow-derived dendritic cells through TLR4 signaling pathway

“…The suboptimal maturation of DCs, which expressed low levels of co-stimulatory and MHC molecules and Th1-polarizing cytokine IL-12, is the one of the reason that caused the limited success of DCbased vaccine in clinical trials [39][40][41]. It has reported that extracts of herbal medicines can enhance anti-tumor immune responses through promoting the maturation and function of DCs [14][15][16][17]. Here, we found that PFWE not only enhanced the maturation of DCs and but also increased the production of IL-12.…”

“…Accumulating evidence including ours indicates that herbal medicine and its components can regulate the maturation and function of DCs to promote the Th1 and CTL responses [12][13][14][15]. Elluru et al [16] showed that aqueous extracts from Viscum album stimulate the maturation and activation of human DCs, which may facilitate anti-tumoral immune responses.…”

Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1

“…DCs generated in this manner were mainly immature DCs (85% of cells are CD11c + ) and displayed the typical morphologic features of DCs. [66]…”

“…Activation of bone marrow-derived DCs (BMDCs) was performed as previously described [66]. Briefly, BMDCs were incubated for 2 h with various test tumor cell lysate (TCL) samples containing 200 μg protein/ml.…”

“…Tumor cell lysate samples were prepared as previously described [8, 66]. To assay for expression of ICD-associated markers, 4T1 TCL protein samples were resolved by SDS PAGE using 8, 10 or 15% stepwise gels.…”