Oncotarget

Research Papers:

A high-throughput customized cytokinome screen of colon cancer cell responses to small-molecule oncology drugs

Kelsey E. Huntington, Anna Louie, Lanlan Zhou and Wafik S. El-Deiry _

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Oncotarget. 2021; 12:1980-1991. https://doi.org/10.18632/oncotarget.28079

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Abstract

Kelsey E. Huntington1,2,3,4,5, Anna Louie1,2,3,6, Lanlan Zhou1,2,3,4 and Wafik S. El-Deiry1,2,3,4,5

1 Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

2 The Joint Program in Cancer Biology, Brown University and Lifespan Health System, Providence, RI 02912, USA

3 Cancer Center at Brown University, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

4 Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

5 Pathobiology Graduate Program, Brown University, Providence, RI 02912, USA

6 Department of Surgery, Brown University, Lifespan Health System and Warren, Alpert Medical School, Brown University, Providence, RI 02912, USA

Correspondence to:

Wafik S. El-Deiry, email: wafik@brown.edu

Keywords: cytokine profiling; inflammatory response; chemokine; growth factor; immune profiling

Received: August 07, 2021     Accepted: September 03, 2021     Published: September 28, 2021

Copyright: © 2021 Huntington et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Inflammatory cytokines, chemokines, and growth factors are molecular messengers that circulate and have the capability to modify the tumor microenvironment and impact therapeutic response. The characterization of soluble mediators as biomarkers for diagnosis and prognosis is of interest in oncology. We utilize the cytokinome to characterize the response of colorectal tumor cell lines to selected small-molecules in oncology as a proof-of-concept dataset with immunomodulatory analyte heat map rankings for drug and cell line combinations. We observed overall trends in drug class effects with MEK-, BRAF-, PARP-inhibitors, and Imipridones in cytokine, chemokine, and growth factor responses that may help guide therapy selection. MEK-inhibitor treatment downregulated analytes VEGF, CXCL9/MIG, and IL-8/CXCL8 and upregulated CXCL14/BRAK, Prolactin, and CCL5/RANTES. BRAF-inhibitor treatment downregulated VEGF and IL-8/CXCL8, while increasing soluble TRAIL-R2. Treatment with PARP-inhibitors decreased CXCL9/MIG, IL-8/CXCL8, CCL3/MIP-1 alpha, VEGF, and CXCL14/BRAK, while treatment increased soluble TRAIL-R2 and prolactin. Treatment with Imipridones decreased CCL3/MIP-1 alpha, VEGF, CXCL14/BRAK, IL-8/CXCL8, and Prolactin and increased CXCL5/ENA-78. We also observed differential responses to therapeutics depending on the mutational profile of the cell line. In the future, a similar but larger dataset may be utilized in the clinic to aid in the prediction of patient response to immunomodulatory therapies based on tumor genotype.


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