A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours

Lilian L. Nohara,Lilian L. Nohara,Lilian L. Nohara, Samantha L. S. Ellis, Samantha L. S. Ellis, Samantha L. S. Ellis, Samantha L. S. Ellis, Carola Dreier, Carola Dreier, Carola Dreier,Sarah Dada,Sarah Dada,Sarah Dada,Sarah Dada,Sarah Dada,Sarah Dada,Iryna Saranchova,Iryna Saranchova,Iryna Saranchova,Iryna Saranchova,Iryna Saranchova,Iryna Saranchova,Lonna Munro,Lonna Munro,Lonna Munro,Lonna Munro,Cheryl G. Pfeifer,Cheryl G. Pfeifer,Cheryl G. Pfeifer,Cheryl G. Pfeifer,Krysta M. Coyle,Krysta M. Coyle,Krysta M. Coyle,Krysta M. Coyle,Krysta M. Coyle, Jessica R. Morrice, Jessica R. Morrice, Jessica R. Morrice, Jessica R. Morrice, Jessica R. Morrice, Daniel Joo Sung Shim, Daniel Joo Sung Shim, Daniel Joo Sung Shim, Daniel Joo Sung Shim, Paul Ahn, Paul Ahn, Paul Ahn, Paul Ahn, Paul Ahn,Nicole De Voogd,David E. Williams,Ping Cheng,Emmanuel Garrovillas,Emmanuel Garrovillas,Raymond J. Andersen,Wilfred A. Jefferies,Wilfred A. Jefferies,Wilfred A. Jefferies,Wilfred A. Jefferies,Wilfred A. Jefferies,Wilfred A. Jefferies

Frontiers in Pharmacology(2023)

引用 3|浏览24
暂无评分
摘要
Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subvert host immune surveillance allowing cancer cells to become invisible to the immune system and, in turn, promote cancer metastasis. Here we describe and validate the first high-throughput cell-based screening assay to identify chemical extracts and unique chemical entities that reverse the downregulation of APM components in cell lines derived from metastatic tumours. Through the screening of a library of 480 marine invertebrate extracts followed by bioassay-guided fractionation, curcuphenol, a common sesquiterpene phenol derived from turmeric, was identified as the active compound of one of the extracts. We demonstrate that curcuphenol induces the expression of the APM components, TAP-1 and MHC-I molecules, in cell lines derived from both metastatic prostate and lung carcinomas. Turmeric and curcumins that contain curcuphenol have long been utilized not only as a spice in the preparation of food, but also in traditional medicines for treating cancers. The remarkable discovery that a common component of spices can increase the expression of APM components in metastatic tumour cells and, therefore reverse immune-escape mechanisms, provides a rationale for the development of foods and advanced nutraceuticals as therapeutic candidates for harnessing the power of the immune system to recognize and destroy metastatic cancers.
更多
查看译文
关键词
antigen processing machinery, curcuphenol, major histocompatibility complex class I, metastatic tumours, natural products, high throughput cell-based assay, drug discovery
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要