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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6631458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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