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Oncotarget: Cytokinome screen of colon cancer cell responses to oncology drugs

There exists a degree of heterogeneity in the prognostic value of cytokines, with some showing opposing correlations in response to therapy across multiple tumor types

Peer-Reviewed Publication

Impact Journals LLC

Figure 7

image: Heatmaps displaying regression slopes of cytokine profiles for Imipridones. (A) Heat maps based on regression slopes for HCT-116, HT-29, and KM12C after 48-hour treatment of increasing doses of ONC201, (B) ONC206, or (C) ONC212. view more 

Credit: Correspondence to - Wafik S. El-Deiry -

Oncotarget published "A high-throughput customized cytokinome screen of colon cancer cell responses to small-molecule oncology drugs" which reported that the characterization of soluble mediators as biomarkers for diagnosis and prognosis is of interest in oncology.

These authors 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. Treatment with Imipridones decreased CCL3/MIP-1 alpha, VEGF, CXCL14/BRAK, IL-8/CXCL8, and Prolactin and increased CXCL5/ENA-78. They 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.

Dr. Wafik S. El-Deiry from The Brown University as well as The Lifespan Health System said, "Cytokines, chemokines, and growth factors are all molecular messengers of the immune system that impact tumor behavior and host response."

Cytokines are either secreted or membrane-bound proteins that regulate cellular signaling and can be categorized as pro- or anti-inflammatory. In CRC, differentially expressed plasma or serum cytokines represent potential biomarkers for diagnosis and prognosis. The levels of cytokines in plasma varied significantly between patients with CRC and control subjects. However, cytokine signaling is highly pleotropic with one cytokine producing diverse and sometimes opposing effects depending on the signaling context.

Moreover, cytokine signaling is characterized by a high degree of redundancy where discrete cytokines produce the same functional effects. The combination of pleotropic and redundant outcomes in response to a particular cytokine makes therapeutic manipulation challenging. Furthermore, there exists a degree of heterogeneity in the prognostic value of cytokines, with some showing opposing correlations in response to therapy across multiple tumor types.

The El-Deiry Research Team concluded in their Oncotarget Research Output that they observed heterogeneity in cytokine, chemokine, and growth factor responses across cell lines and across drug treatments. When the results were grouped by either analytes that are correlated with immunosuppression or unfavorable prognosis or by analytes that are correlated with immunostimulation or favorable prognosis, they found that it was difficult to make clear predictions about which combinations of therapeutics would promote anti-tumor immunity in the context of CRC. However, this dataset is limited and perhaps clearer trends would emerge with a greater sample size. Moreover, this dataset is amenable to building a larger database with other cytokinome data. Future studies can focus on specific cell lines, tumor types, classes of drugs, and subsets of cytokines.

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Correspondence to - Wafik S. El-Deiry -

Keywords - cytokine profilinginflammatory responsechemokinegrowth factorimmune profiling

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