Cargando…
Inhibition of IL-18-mediated myeloid derived suppressor cell accumulation enhances anti-PD1 efficacy against osteosarcoma cancer
Myeloid derived suppressor cells (MDSC) are very important in tumor immune evasion and they dramatically increased in peripheral blood of patients with osteosarcoma cancer. The association between MDSC and various cytokines has been studied in the peripheral blood. However, little is known about the...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715437/ https://www.ncbi.nlm.nih.gov/pubmed/29226090 http://dx.doi.org/10.1016/j.jbo.2017.10.002 |
_version_ | 1783283768219402240 |
---|---|
author | Guan, Ying Zhang, Rui Peng, Zhibin Dong, Daming Wei, Guojun Wang, Yansong |
author_facet | Guan, Ying Zhang, Rui Peng, Zhibin Dong, Daming Wei, Guojun Wang, Yansong |
author_sort | Guan, Ying |
collection | PubMed |
description | Myeloid derived suppressor cells (MDSC) are very important in tumor immune evasion and they dramatically increased in peripheral blood of patients with osteosarcoma cancer. The association between MDSC and various cytokines has been studied in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and interleukin 18 (IL-18) level in osteosarcoma tumor model and its effect on the immunotherapy. MDSC were isolated from the blood and parenchyma and analyzed in the osteosarcoma tumor model. IL-18 levels were detected by enzyme-linked immunosorbent assay (ELISA) assay, real-time PCR, western blot and flow cytometry. Moreover, combination treatment with IL-18 inhibition and anti-PD1 was conducted to assess the therapeutic effects of IL-18 blockade. Results showed MDSC levels had a positive correlation with IL-18, suggesting IL-18 may attract MDSC into the parenchyma. IL-18 gene and protein expression significantly increased in blood and tumor lysates of tumor-bearing mice. Anti-IL-18 treatment significantly decreased G-MDSC and M-MDSC in the peripheral blood and tumor. Furthermore, combination therapy decreased the tumor burden and increased CD4(+) and CD8(+) T cell infiltration, as well as the production of interferon gamma (IFNγ) and granzyme B. Our study revealed a possible correlation between MDSC subsets and IL-18 inducing MDSC migration into the tumor tissue, in addition to provide the potential target to enhance the efficacy of immunotherapy in patients with osteosarcoma. |
format | Online Article Text |
id | pubmed-5715437 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-57154372017-12-08 Inhibition of IL-18-mediated myeloid derived suppressor cell accumulation enhances anti-PD1 efficacy against osteosarcoma cancer Guan, Ying Zhang, Rui Peng, Zhibin Dong, Daming Wei, Guojun Wang, Yansong J Bone Oncol Research Article Myeloid derived suppressor cells (MDSC) are very important in tumor immune evasion and they dramatically increased in peripheral blood of patients with osteosarcoma cancer. The association between MDSC and various cytokines has been studied in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and interleukin 18 (IL-18) level in osteosarcoma tumor model and its effect on the immunotherapy. MDSC were isolated from the blood and parenchyma and analyzed in the osteosarcoma tumor model. IL-18 levels were detected by enzyme-linked immunosorbent assay (ELISA) assay, real-time PCR, western blot and flow cytometry. Moreover, combination treatment with IL-18 inhibition and anti-PD1 was conducted to assess the therapeutic effects of IL-18 blockade. Results showed MDSC levels had a positive correlation with IL-18, suggesting IL-18 may attract MDSC into the parenchyma. IL-18 gene and protein expression significantly increased in blood and tumor lysates of tumor-bearing mice. Anti-IL-18 treatment significantly decreased G-MDSC and M-MDSC in the peripheral blood and tumor. Furthermore, combination therapy decreased the tumor burden and increased CD4(+) and CD8(+) T cell infiltration, as well as the production of interferon gamma (IFNγ) and granzyme B. Our study revealed a possible correlation between MDSC subsets and IL-18 inducing MDSC migration into the tumor tissue, in addition to provide the potential target to enhance the efficacy of immunotherapy in patients with osteosarcoma. Elsevier 2017-11-01 /pmc/articles/PMC5715437/ /pubmed/29226090 http://dx.doi.org/10.1016/j.jbo.2017.10.002 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Guan, Ying Zhang, Rui Peng, Zhibin Dong, Daming Wei, Guojun Wang, Yansong Inhibition of IL-18-mediated myeloid derived suppressor cell accumulation enhances anti-PD1 efficacy against osteosarcoma cancer |
title | Inhibition of IL-18-mediated myeloid derived suppressor cell accumulation enhances anti-PD1 efficacy against osteosarcoma cancer |
title_full | Inhibition of IL-18-mediated myeloid derived suppressor cell accumulation enhances anti-PD1 efficacy against osteosarcoma cancer |
title_fullStr | Inhibition of IL-18-mediated myeloid derived suppressor cell accumulation enhances anti-PD1 efficacy against osteosarcoma cancer |
title_full_unstemmed | Inhibition of IL-18-mediated myeloid derived suppressor cell accumulation enhances anti-PD1 efficacy against osteosarcoma cancer |
title_short | Inhibition of IL-18-mediated myeloid derived suppressor cell accumulation enhances anti-PD1 efficacy against osteosarcoma cancer |
title_sort | inhibition of il-18-mediated myeloid derived suppressor cell accumulation enhances anti-pd1 efficacy against osteosarcoma cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715437/ https://www.ncbi.nlm.nih.gov/pubmed/29226090 http://dx.doi.org/10.1016/j.jbo.2017.10.002 |
work_keys_str_mv | AT guanying inhibitionofil18mediatedmyeloidderivedsuppressorcellaccumulationenhancesantipd1efficacyagainstosteosarcomacancer AT zhangrui inhibitionofil18mediatedmyeloidderivedsuppressorcellaccumulationenhancesantipd1efficacyagainstosteosarcomacancer AT pengzhibin inhibitionofil18mediatedmyeloidderivedsuppressorcellaccumulationenhancesantipd1efficacyagainstosteosarcomacancer AT dongdaming inhibitionofil18mediatedmyeloidderivedsuppressorcellaccumulationenhancesantipd1efficacyagainstosteosarcomacancer AT weiguojun inhibitionofil18mediatedmyeloidderivedsuppressorcellaccumulationenhancesantipd1efficacyagainstosteosarcomacancer AT wangyansong inhibitionofil18mediatedmyeloidderivedsuppressorcellaccumulationenhancesantipd1efficacyagainstosteosarcomacancer |