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IL-6 and IL-8 Are Linked With Myeloid-Derived Suppressor Cell Accumulation and Correlate With Poor Clinical Outcomes in Melanoma Patients
We sought to identify tumor-secreted factors that altered the frequency of MDSCs and correlated with clinical outcomes in advanced melanoma patients. We focused our study on several of the many factors involved in the expansion and mobilization of MDSCs. These were identified by measuring circulatin...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857649/ https://www.ncbi.nlm.nih.gov/pubmed/31781510 http://dx.doi.org/10.3389/fonc.2019.01223 |
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author | Tobin, Richard P. Jordan, Kimberly R. Kapoor, Puja Spongberg, Eric Davis, Dana Vorwald, Victoria M. Couts, Kasey L. Gao, Dexiang Smith, Derek E. Borgers, Jessica S. W. Robinson, Steven Amato, Carol Gonzalez, Rene Lewis, Karl D. Robinson, William A. Borges, Virginia F. McCarter, Martin D. |
author_facet | Tobin, Richard P. Jordan, Kimberly R. Kapoor, Puja Spongberg, Eric Davis, Dana Vorwald, Victoria M. Couts, Kasey L. Gao, Dexiang Smith, Derek E. Borgers, Jessica S. W. Robinson, Steven Amato, Carol Gonzalez, Rene Lewis, Karl D. Robinson, William A. Borges, Virginia F. McCarter, Martin D. |
author_sort | Tobin, Richard P. |
collection | PubMed |
description | We sought to identify tumor-secreted factors that altered the frequency of MDSCs and correlated with clinical outcomes in advanced melanoma patients. We focused our study on several of the many factors involved in the expansion and mobilization of MDSCs. These were identified by measuring circulating concentrations of 13 cytokines and growth factors in stage IV melanoma patients (n = 55) and healthy controls (n = 22). Based on these results, we hypothesized that IL-6 and IL-8 produced by melanoma tumor cells participate in the expansion and recruitment of MDSCs and together would be predictive of overall survival in melanoma patients. We then compared the expression of IL-6 and IL-8 in melanoma tumors to the corresponding plasma concentrations and the frequency of circulating MDSCs. These measures were correlated with clinical outcomes. Patients with high plasma concentrations of either IL-6 (40%) or IL-8 (63%), or both (35%) had worse median overall survival compared to patients with low concentrations. Patients with low peripheral concentrations and low tumoral expression of IL-6 and IL-8 showed decreased frequencies of circulating MDSCs, and patients with low frequencies of MDSCs had better overall survival. We have previously shown that IL-6 is capable of expanding MDSCs, and here we show that MDSCs are chemoattracted to IL-8. Multivariate analysis demonstrated an increased risk of death for subjects with both high IL-6 and IL-8 (HR 3.059) and high MDSCs (HR 4.265). Together these results indicate an important role for IL-6 and IL-8 in melanoma patients in which IL-6 potentially expands peripheral MDSCs and IL-8 recruits these highly immunosuppressive cells to the tumor microenvironment. This study provides further support for identifying potential therapeutics targeting IL-6, IL-8, and MDSCs to improve melanoma treatments. |
format | Online Article Text |
id | pubmed-6857649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68576492019-11-28 IL-6 and IL-8 Are Linked With Myeloid-Derived Suppressor Cell Accumulation and Correlate With Poor Clinical Outcomes in Melanoma Patients Tobin, Richard P. Jordan, Kimberly R. Kapoor, Puja Spongberg, Eric Davis, Dana Vorwald, Victoria M. Couts, Kasey L. Gao, Dexiang Smith, Derek E. Borgers, Jessica S. W. Robinson, Steven Amato, Carol Gonzalez, Rene Lewis, Karl D. Robinson, William A. Borges, Virginia F. McCarter, Martin D. Front Oncol Oncology We sought to identify tumor-secreted factors that altered the frequency of MDSCs and correlated with clinical outcomes in advanced melanoma patients. We focused our study on several of the many factors involved in the expansion and mobilization of MDSCs. These were identified by measuring circulating concentrations of 13 cytokines and growth factors in stage IV melanoma patients (n = 55) and healthy controls (n = 22). Based on these results, we hypothesized that IL-6 and IL-8 produced by melanoma tumor cells participate in the expansion and recruitment of MDSCs and together would be predictive of overall survival in melanoma patients. We then compared the expression of IL-6 and IL-8 in melanoma tumors to the corresponding plasma concentrations and the frequency of circulating MDSCs. These measures were correlated with clinical outcomes. Patients with high plasma concentrations of either IL-6 (40%) or IL-8 (63%), or both (35%) had worse median overall survival compared to patients with low concentrations. Patients with low peripheral concentrations and low tumoral expression of IL-6 and IL-8 showed decreased frequencies of circulating MDSCs, and patients with low frequencies of MDSCs had better overall survival. We have previously shown that IL-6 is capable of expanding MDSCs, and here we show that MDSCs are chemoattracted to IL-8. Multivariate analysis demonstrated an increased risk of death for subjects with both high IL-6 and IL-8 (HR 3.059) and high MDSCs (HR 4.265). Together these results indicate an important role for IL-6 and IL-8 in melanoma patients in which IL-6 potentially expands peripheral MDSCs and IL-8 recruits these highly immunosuppressive cells to the tumor microenvironment. This study provides further support for identifying potential therapeutics targeting IL-6, IL-8, and MDSCs to improve melanoma treatments. Frontiers Media S.A. 2019-11-08 /pmc/articles/PMC6857649/ /pubmed/31781510 http://dx.doi.org/10.3389/fonc.2019.01223 Text en Copyright © 2019 Tobin, Jordan, Kapoor, Spongberg, Davis, Vorwald, Couts, Gao, Smith, Borgers, Robinson, Amato, Gonzalez, Lewis, Robinson, Borges and McCarter. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Tobin, Richard P. Jordan, Kimberly R. Kapoor, Puja Spongberg, Eric Davis, Dana Vorwald, Victoria M. Couts, Kasey L. Gao, Dexiang Smith, Derek E. Borgers, Jessica S. W. Robinson, Steven Amato, Carol Gonzalez, Rene Lewis, Karl D. Robinson, William A. Borges, Virginia F. McCarter, Martin D. IL-6 and IL-8 Are Linked With Myeloid-Derived Suppressor Cell Accumulation and Correlate With Poor Clinical Outcomes in Melanoma Patients |
title | IL-6 and IL-8 Are Linked With Myeloid-Derived Suppressor Cell Accumulation and Correlate With Poor Clinical Outcomes in Melanoma Patients |
title_full | IL-6 and IL-8 Are Linked With Myeloid-Derived Suppressor Cell Accumulation and Correlate With Poor Clinical Outcomes in Melanoma Patients |
title_fullStr | IL-6 and IL-8 Are Linked With Myeloid-Derived Suppressor Cell Accumulation and Correlate With Poor Clinical Outcomes in Melanoma Patients |
title_full_unstemmed | IL-6 and IL-8 Are Linked With Myeloid-Derived Suppressor Cell Accumulation and Correlate With Poor Clinical Outcomes in Melanoma Patients |
title_short | IL-6 and IL-8 Are Linked With Myeloid-Derived Suppressor Cell Accumulation and Correlate With Poor Clinical Outcomes in Melanoma Patients |
title_sort | il-6 and il-8 are linked with myeloid-derived suppressor cell accumulation and correlate with poor clinical outcomes in melanoma patients |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857649/ https://www.ncbi.nlm.nih.gov/pubmed/31781510 http://dx.doi.org/10.3389/fonc.2019.01223 |
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