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

Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Nohara, Lilian L.;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Ellis, Samantha L. S.;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Dreier, Carola;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Dada, Sarah;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Saranchova, Iryna;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Choi, Kyong Bok;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Munro, Lonna;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Pfeifer, Cheryl G.;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Al Haddad, Eliana;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Coyle, Krysta M.;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Morrice, Jessica R.;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Shim, Daniel Joo Sung;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Ahn, Paul;
Affiliation
Netherlands Centre for Biodiversity Naturalis ,Leiden ,Netherlands
De Voogd, Nicole;
Affiliation
Departments of Chemistry and Earth Ocean and Atmospheric Sciences ,University of British Columbia ,Vancouver ,BC ,Canada
Williams, David E.;
Affiliation
Departments of Chemistry and Earth Ocean and Atmospheric Sciences ,University of British Columbia ,Vancouver ,BC ,Canada
Cheng, Ping;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Garrovillas, Emmanuel;
Affiliation
Departments of Chemistry and Earth Ocean and Atmospheric Sciences ,University of British Columbia ,Vancouver ,BC ,Canada
Andersen, Raymond J.;
Affiliation
Michael Smith Laboratories ,University of British Columbia ,Vancouver ,BC ,Canada
Jefferies, Wilfred A.

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.

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License Holder: Copyright © 2023 Nohara, Ellis, Dreier, Dada, Saranchova, Choi, Munro, Pfeifer, Al Haddad, Coyle, Morrice, Shim, Ahn, De Voogd, Williams, Cheng, Garrovillas, Andersen and Jefferies.

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