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Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells

1
College of Veterinary Medicine, Tuskegee University, Tuskegee, AL 36088, USA
2
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
Medicines 2019, 6(2), 51; https://doi.org/10.3390/medicines6020051
Received: 6 March 2019 / Revised: 16 April 2019 / Accepted: 19 April 2019 / Published: 24 April 2019
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Abstract

Background: Immunotherapy has changed the options for the treatment of various cancer types, but not colon cancer. Current checkpoint blockade approaches are ineffective in a large proportion of colon cancer cases, necessitating studies to elucidate its mechanisms and to identify new targets and strategies against it. Methods: Here, we examined Programmed Death-Ligand 1(PD-L1), cytokine and receptor responses of colon cancer cells exposed to camptothecin (CPT), a clinically used topoisomerase inhibitor. Colon cancer cells were treated with CPT at concentrations of up to 10 µM, and the expressions of PD-L1 and immunoregulatory cytokine genes and receptors were analyzed. Results: PD-L1, a current immunotherapy target for various cancers, was shown to be upregulated in colon cancer cells independent of the cellular p53 status. In metastasis-derived SW620 cells, CPT most extensively upregulated cytokines with T-cell attraction or growth factor functions. Of those modulated genes, SPP1, IL1RN, IL1A, TNFSF13B, OSM, and CSF3 had the most clinical relevance, as their high expression was associated with poor cancer patient overall survival. Conclusions: These findings highlight the need to examine, in preclinical and clinical situations, the potential benefits of combining topoisomerase inhibitors with immune-checkpoint inhibitors. View Full-Text
Keywords: camptothecin; colon cancer; cytokine; PD-L1; immunotherapy; topoisomerase inhibition camptothecin; colon cancer; cytokine; PD-L1; immunotherapy; topoisomerase inhibition
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Bedi, D.; Henderson, H.J.; Manne, U.; Samuel, T. Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells. Medicines 2019, 6, 51.

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