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Circulating and Tumor-Infiltrating Myeloid-Derived Suppressor Cells in Patients with Colorectal Carcinoma

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T cell immunity in tumor-bearing hosts. In patients with colon cancer, MDSCs have recently been described as Lin(−/low)HLA-DR(−)CD11b(+)CD33(+) cells correlating with cancer stage, metastasis and chemo...

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Autores principales: Zhang, Bin, Wang, Zhijun, Wu, Liangliang, Zhang, Meng, Li, Wei, Ding, Jianhua, Zhu, Jun, Wei, Huafeng, Zhao, Ke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577767/
https://www.ncbi.nlm.nih.gov/pubmed/23437326
http://dx.doi.org/10.1371/journal.pone.0057114
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author Zhang, Bin
Wang, Zhijun
Wu, Liangliang
Zhang, Meng
Li, Wei
Ding, Jianhua
Zhu, Jun
Wei, Huafeng
Zhao, Ke
author_facet Zhang, Bin
Wang, Zhijun
Wu, Liangliang
Zhang, Meng
Li, Wei
Ding, Jianhua
Zhu, Jun
Wei, Huafeng
Zhao, Ke
author_sort Zhang, Bin
collection PubMed
description Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T cell immunity in tumor-bearing hosts. In patients with colon cancer, MDSCs have recently been described as Lin(−/low)HLA-DR(−)CD11b(+)CD33(+) cells correlating with cancer stage, metastasis and chemotherapy response. To learn in more detail the dynamic change and clinical relevance of circulating and tumor-infiltrating Lin(−/low)HLA-DR(−)CD11b(+)CD33(+) MDSC in colorectal cancer, we harvested the blood from 64 patients with varying stage of colorectal cancer and tumor and matched paraneoplastic tissues from 5 patients with advanced colorectal cancer, subjected them to multicolor flow cytometric analysis of percentage, absolute number and phenotype of MDSC and finally characterized their immunosuppressive functions. Our results demonstrate that peripheral blood from colorectal cancer patients contains markedly increased percentage and absolute number of Lin(−/low)HLA-DR(−)CD11b(+)CD33(+) MDSCs compared with healthy individuals, and this increase is closely correlated with clinical cancer stage and tumor metastasis but not primary tumor size and serum concentrations of cancer biomarker. A similar increase of MDSCs was also observed in the tumor tissues. Phenotyping MDSCs shows that they express high CD13 and CD39, low CD115, CD117, CD124 and PD-L1, and devoid of CD14, CD15 and CD66b, reminiscent of precursor myeloid cells. MDSCs from cancer patients but not healthy donors have the immunosuppressive activity and were able to inhibit in vitro autologous T-cell proliferation. Collectively, this study substantiates the presence of increased immunosuppressive circulating and tumor-resident Lin(−/low)HLA-DR(−)CD11b(+)CD33(+) MDSCs in patients with colorectal cancers correlating with cancer stage and metastasis, and suggests that pharmacologic blockade of MDSCs should be considered in future clinical trials.
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spelling pubmed-35777672013-02-22 Circulating and Tumor-Infiltrating Myeloid-Derived Suppressor Cells in Patients with Colorectal Carcinoma Zhang, Bin Wang, Zhijun Wu, Liangliang Zhang, Meng Li, Wei Ding, Jianhua Zhu, Jun Wei, Huafeng Zhao, Ke PLoS One Research Article Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T cell immunity in tumor-bearing hosts. In patients with colon cancer, MDSCs have recently been described as Lin(−/low)HLA-DR(−)CD11b(+)CD33(+) cells correlating with cancer stage, metastasis and chemotherapy response. To learn in more detail the dynamic change and clinical relevance of circulating and tumor-infiltrating Lin(−/low)HLA-DR(−)CD11b(+)CD33(+) MDSC in colorectal cancer, we harvested the blood from 64 patients with varying stage of colorectal cancer and tumor and matched paraneoplastic tissues from 5 patients with advanced colorectal cancer, subjected them to multicolor flow cytometric analysis of percentage, absolute number and phenotype of MDSC and finally characterized their immunosuppressive functions. Our results demonstrate that peripheral blood from colorectal cancer patients contains markedly increased percentage and absolute number of Lin(−/low)HLA-DR(−)CD11b(+)CD33(+) MDSCs compared with healthy individuals, and this increase is closely correlated with clinical cancer stage and tumor metastasis but not primary tumor size and serum concentrations of cancer biomarker. A similar increase of MDSCs was also observed in the tumor tissues. Phenotyping MDSCs shows that they express high CD13 and CD39, low CD115, CD117, CD124 and PD-L1, and devoid of CD14, CD15 and CD66b, reminiscent of precursor myeloid cells. MDSCs from cancer patients but not healthy donors have the immunosuppressive activity and were able to inhibit in vitro autologous T-cell proliferation. Collectively, this study substantiates the presence of increased immunosuppressive circulating and tumor-resident Lin(−/low)HLA-DR(−)CD11b(+)CD33(+) MDSCs in patients with colorectal cancers correlating with cancer stage and metastasis, and suggests that pharmacologic blockade of MDSCs should be considered in future clinical trials. Public Library of Science 2013-02-20 /pmc/articles/PMC3577767/ /pubmed/23437326 http://dx.doi.org/10.1371/journal.pone.0057114 Text en © 2013 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhang, Bin
Wang, Zhijun
Wu, Liangliang
Zhang, Meng
Li, Wei
Ding, Jianhua
Zhu, Jun
Wei, Huafeng
Zhao, Ke
Circulating and Tumor-Infiltrating Myeloid-Derived Suppressor Cells in Patients with Colorectal Carcinoma
title Circulating and Tumor-Infiltrating Myeloid-Derived Suppressor Cells in Patients with Colorectal Carcinoma
title_full Circulating and Tumor-Infiltrating Myeloid-Derived Suppressor Cells in Patients with Colorectal Carcinoma
title_fullStr Circulating and Tumor-Infiltrating Myeloid-Derived Suppressor Cells in Patients with Colorectal Carcinoma
title_full_unstemmed Circulating and Tumor-Infiltrating Myeloid-Derived Suppressor Cells in Patients with Colorectal Carcinoma
title_short Circulating and Tumor-Infiltrating Myeloid-Derived Suppressor Cells in Patients with Colorectal Carcinoma
title_sort circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577767/
https://www.ncbi.nlm.nih.gov/pubmed/23437326
http://dx.doi.org/10.1371/journal.pone.0057114
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