Circulating myeloid-derived suppressor cells are increased and correlate to immune suppression, inflammation and hypoproteinemia in patients with cancer

Ohki,Shinji; Shibata,Masahiko; Gonda,Kenji; Machida,Takeshi; Shimura,Tatsuo; Nakamura,Izumi; Ohtake,Toru; Koyama,Yoshihisa; Suzuki,Shinichi; Ohto,Hitoshi; Takenoshita,Seiichi

doi:10.3892/or.2012.1812

August 2012 Volume 28 Issue 2

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August 2012 Volume 28 Issue 2

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Article

Circulating myeloid-derived suppressor cells are increased and correlate to immune suppression, inflammation and hypoproteinemia in patients with cancer

Authors:
- Shinji Ohki
- Masahiko Shibata
- Kenji Gonda
- Takeshi Machida
- Tatsuo Shimura
- Izumi Nakamura
- Toru Ohtake
- Yoshihisa Koyama
- Shinichi Suzuki
- Hitoshi Ohto
- Seiichi Takenoshita
View Affiliations / Copyright

Affiliations: Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan, Department of Tumor and Host Bioscience, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan, Department of Immunology, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan, Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan
Pages: 453-458
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Published online on: May 14, 2012

https://doi.org/10.3892/or.2012.1812
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Abstract

Recent studies have identified myeloid-derived suppressor cells (MDSCs) that are potent suppressors of tumor immunity and therefore a significant impediment to cancer immunotherapy. It has been reported that MDSCs are generated by malignant diseases or inflammation. However, no systematic studies in patients have been described. In order to clinically characterize MDSCs, we tested PBMCs from patients with various types of cancer including cholangiocellular, hepatocellular and pancreatic carcinoma, esophageal, gastric and colorectal cancer, breast cancer and thyroid cancer, and GIST, and those from normal volunteers using flow cytometry analysis. A significant increase was seen in the percentages of MDSCs in PBMCs from patients compared with normal volunteers. Among these patients, MDSC level was higher in patients with cancer of the digestive system and patients with breast cancer compared with normal volunteers. MDSC level was significantly and inversely correlated to stimulation indices (SI) of PHA-blastogenesis of lymphocytes and serum concentration of total protein, and positively correlated to neutrophil count. MDSC percentage in patients with gastric and colorectal cancer was also significantly correlated to neutrophil count and inversely correlated with lymphocyte count, and showed highly significant correlation to neutrophil/lymphocyte rate (NLR). In patients with breast cancer, MDSC levels in preoperative patients was significantly increased compared to normal volunteers and significantly decreased in postoperative patients. Thus, it is clear that MDSCs are increased in patients with cancer and closely related to suppression of cell-mediated immune responses. These data also suggest that they are related to chronic inflammation and that their levels are increased further in the terminal stages of patients whose nutritional status is impaired as observed in hypoproteinemia. MDSC levels have also been shown to decrease after removal of tumors in patients with breast cancer.

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1	Rosenberg SA, Yang JC and Restifo NP: Cancer immunotherapy: moving beyond current vaccines. Nat Med. 10:909–915. 2004. View Article : Google Scholar : PubMed/NCBI
2	Pardoll D and Allison J: Cancer immunotherapy: breaking the barriers to harvest the crop. Nat Med. 10:887–902. 2004. View Article : Google Scholar : PubMed/NCBI
3	Gabrilovich DI and Nagaj S: Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 9:162–174. 2009. View Article : Google Scholar : PubMed/NCBI
4	Rosenberg SO and Sinha P: Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol. 182:4499–4506. 2009. View Article : Google Scholar : PubMed/NCBI
5	Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, McDermott D, Quiceno D, Youmans A, O’Neill A and Ochoa AC: Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res. 65:3044–3048. 2005.PubMed/NCBI
6	Ochoa AC, Zea AH, Hernandez C and Rodriguez PC: Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res. 13:S721–S726. 2007. View Article : Google Scholar : PubMed/NCBI
7	Diaz-Montero CM, Salem ML, Nishimura MI, Garett-Mayre E, Cole DJ and Montero AJ: Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother. 58:49–59. 2009. View Article : Google Scholar
8	Gabitass RF, Annels NE, Crawshaw J, Pandha HS and Middleton GE: Use of gemcitabine-(GEM) and fluoropyrimidine-based chemotherapy to reduce myeloid-derived suppressor cells (MDSCs) in pancreatic (PC) and esophagogastric cancer (EGC). J Clin Oncol. 29:25882011.
9	Kusmartsev S, Nefedova Y, Yoder D and Gabrilovich DI: Antigen-specific inhibition of CD8⁺ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol. 172:989–999. 2004.PubMed/NCBI
10	Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP and Gabrilovich DI: Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 166:678–689. 2001. View Article : Google Scholar : PubMed/NCBI
11	Blackwill F and Mantovani A: Cancer and inflammation: implications for pharmacology and therapeutics. Clin Pharmacol Ther. 87:401–406. 2010. View Article : Google Scholar
12	Gabrilovich DI, Chen HL, Girgis KR, Cinninghan HT, Meny GM, Nadaf S, Kavanauch D and Carbone DP: Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med. 2:1096–1099. 1996. View Article : Google Scholar : PubMed/NCBI
13	Menetrier-Caux C, Montmain G, Dieu MC, Bain C, Favrot MC, Caux C and Blay JY: Inhibition of the differentiation of denderitic cells from CD34⁺ progenitors by tumor cells: role of interleukin-6 and macrophage-colony-stimulating factor. Blood. 92:4778–4791. 1998.PubMed/NCBI
14	Breitman TR, Collins SJ and Keene BR: Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid. Blood. 57:1000–1011. 1981.PubMed/NCBI
15	Coussens LM and Werb Z: Inflammation and cancer. Nature. 420:860–867. 2002. View Article : Google Scholar : PubMed/NCBI
16	Forrest LM, McMillan DC, McArdle CS, Angerson WJ and Dunlop DJ: Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer. 89:1028–1030. 2003. View Article : Google Scholar : PubMed/NCBI
17	Chua W, Charles KA, Baracos VE and Clarke SJ: Neurrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br J Cancer. 104:1288–1295. 2001. View Article : Google Scholar : PubMed/NCBI
18	Cho H, Hur HW, Kim SW, Kim SH, Kim JH, Kim YT and Lee K: Pretreatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment. Cancer Immunol Immunother. 58:15–23. 2009. View Article : Google Scholar : PubMed/NCBI
19	Shibata M, Takekawa M and Amano S: Increased serum concentrations of soluble tumor necrosis factor receptor 1 in noncachectic and cachectic patients with advanced gastric and colorectal cancer. Surg Today. 28:884–888. 1998. View Article : Google Scholar
20	Shibata M and Takekawa M: Increased serum concentration of circulating soluble receptor for interleukin-2 and its effect as a prognostic indicator in cachectic patients with gastric and colorectal cancer. Oncology. 56:54–58. 1999. View Article : Google Scholar
21	Shibata M, Nagata Y, Kimura T, Kanou H, Nezu T and Fukuzawa M: Elevated serum concentration of interleukin-1 receptor antagonist (IL-1ra) is correlated to interleukin-6 and to hypoalbuminemia in cachectic patients with colorectal cancer. Int J Clin Oncol. 5:116–120. 2000. View Article : Google Scholar

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Circulating myeloid-derived suppressor cells are increased and correlate to immune suppression, inflammation and hypoproteinemia in patients with cancer

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Abstract

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