Abstract 2707: Investigation of the immunomodulatory effects of Radix Astragali targeting dendritic cells
Authors: Daniel M. Sze, Foo-tim Chau, Michelle Chun-har Ng, Kei Fan, Tsui-yan Lau, Hoi-yan Chan
Journal: Cancer Research (2011)

Abstract Dendritic Cells play a pivotal role in the regulation of tumour-specific immune responses. However, cancer-associated microenvironment may adversely affect DC-related immune-surveillance system leading to defective DCs, which fail to up-regulate important co-stimulatory surface molecules CD40 and CD80, and consequently ensues tumor escape and tolerogenicity. Since Radix Astragali has been traditionally used to enhance the body's general well-being, we thus hypothesized that compounds from RA may up-regulate CD80 expression on DCs leading to effective anti-cancer immunity in patients. This study aims: 1.) to study the immunomodulatory effect of the RA using our established THP-1-based DC standardized functionality platform; and 2.) to correlate the CD80 and CD40 expression on THP-1 with the corresponding chemical chromatographic profiles using Quantitative Pattern-Activity Relationship (QPAR) method. Different sources of RA in combination with different refluxing time and solvent systems resulting in different fractions were used for DC functionality flow study and LC-DAD-MS chromatographic fingerprinting. The flow cytometric analysis of four fractions is presented here. Negative flow cytometric control was the untreated cell preparation, while the positive control was treated with LPS where both CD40 and CD80 were up-regulated by 87.3% and 43.1%, respectively, compared with untreated counterpart. THP-1 treated with fraction RA-A23 showed the highest up-regulation of CD40 expression (91.0%); whereas that of fraction RA-C8 had the highest CD80 expression (57.3%). For treatments with fraction RA-14 and RA-C8, THP-1 showed an elevated CD80 expression of 45.0% and 57.3% respectively which is higher than that of LPS. Most interestingly, when THP-1 was treated with fraction RA-1, CD40 and CD80 expression were down-regulated by 44.5% and 49.8%, respectively, in comparison to their untreated controls, thus consistent with a tolerogenic immunological effect. We demonstrated that fractions of the same herb may have opposing immunological effects by modulating the CD40 and CD80 expressions. These contrasting immunological effects of different fractions from a single herb may correspond to the chromatographic profiles illustrating different chemical constituents residing in different fractions. QPAR analysis has been then employed to reveal the chemical constituents in relation to the immunomodulatory effects. It is suggested that understanding the interrelationship of the chemical constituents profile and its corresponding effects on DC costimulatory markers expression may provide useful insights of herbal vaccination-adjuvants and further lead to a more effective DC immunotherapy. Furthermore, we have recently established an IL-10/LPS pre-treatment system to delineate the signalling pathways for the effects of our herbal fractions with distinct effects on CD40/CD80 expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2707. doi:10.1158/1538-7445.AM2011-2707