Shikonin-enhanced cell immunogenicity of tumor vaccine is mediated by the differential effects of DAMP components

作者：Tien-Jen Lin, Hsin-Ting Lin, Wei‐Ting Chang, Pradeep Mitapalli. S, Pei‐Wen Hsiao, Shu‐Yi Yin, Ning‐Sun Yang · 发表于：Molecular Cancer · 年份：2015 · DOI：10.1186/s12943-015-0435-9 · 被引用次数：101 · 研究领域：Bioactive Compounds and Antitumor Agents、Immunotherapy and Immune Responses、Synthesis and Biological Evaluation

BACKGROUND: The tumor cell lysate-pulsed, dendritic cell (DC)-based cancer vaccine approaches are being actively evaluated for application to cancer immunotherapy, hopefully at a personalized medicine base. There is apparently an emerging technical problem however, the lack of highly efficacious potency in activation of patient's DCs for T-cell priming and the associated process for presenting tumor immunogenicity. METHODS: One strategy to address this is to consider the manipulation of the tumor immunogenic cells death (ICD) complex ex-vivo for maximal activation of DC efficacy. In our previous study we showed that phytochemical shikonin (SK) can drastically enhance ICD activity in mouse tumor cells treated ex-vivo, and the resultant tumor cell lysate (TCL) can effectively augment such SK-TCL pulsed DC vaccine activity in vivo in anti-tumor activities. In this study, we investigated the specifics and the multi-functional effects of various damaged associated molecular pattern (DAMP) components of the ICD complex for their participation, roles and potential cross talks in activating DCs, as measured by five different functional assays. RESULTS: Among three DAMPs tested, HSP70 and CRT mediate a key role in SK-TCL-induced DC immunity for both CD4(+) and CD8(+) T cell proliferations in vitro. HSP70 is the most important component, followed by CRT, then HMGB1 in facilitating DC immunity on suppressing metastasis of mouse 4 T1 mammary tumors and prolonging survival in test mice. O...