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

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 str...

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Autores principales: Bedi, Deepa, Henderson, Henry J., Manne, Upender, Samuel, Temesgen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631458/
https://www.ncbi.nlm.nih.gov/pubmed/31022845
http://dx.doi.org/10.3390/medicines6020051
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author Bedi, Deepa
Henderson, Henry J.
Manne, Upender
Samuel, Temesgen
author_facet Bedi, Deepa
Henderson, Henry J.
Manne, Upender
Samuel, Temesgen
author_sort Bedi, Deepa
collection PubMed
description 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.
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spelling pubmed-66314582019-08-19 Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells Bedi, Deepa Henderson, Henry J. Manne, Upender Samuel, Temesgen Medicines (Basel) Article 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. MDPI 2019-04-24 /pmc/articles/PMC6631458/ /pubmed/31022845 http://dx.doi.org/10.3390/medicines6020051 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bedi, Deepa
Henderson, Henry J.
Manne, Upender
Samuel, Temesgen
Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells
title Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells
title_full Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells
title_fullStr Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells
title_full_unstemmed Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells
title_short Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells
title_sort camptothecin induces pd-l1 and immunomodulatory cytokines in colon cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631458/
https://www.ncbi.nlm.nih.gov/pubmed/31022845
http://dx.doi.org/10.3390/medicines6020051
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