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

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.

Myeloid-Derived Suppressor Cells Attenuate TH1 Development through IL-6 Production to Promote Tumor Progression

“…The systemic increase of IL-6 levels in the plasma of patients with cancer (28,29) markedly correlated with proportional accumulation of MDSC (30,31). These reports support our findings and previous reports (39,40) that MDSC produce IL-6 in tumor-bearing mice.…”

“…Chronic inflammation and increased levels of inflammatory cytokines including IL-6 have been reported in patients with various type of tumors (26), and an elevated level of IL-6 fostering progressive expansion of tumor cells (27) has been associated with poor clinical outcome (28)(29)(30)(31). Here, we focused on the association between the functional impairment of CD4 þ T cells and immune-suppressive effects of the tumor-induced inflammation-related factors, IL-6 and MDSC.…”

IL-17 and VEGF are significantly associated with disease progression involving systemic inflammation in patients with gastric and colorectal cancers

“…Accumulating evidence [10][11][12][13] suggests that a population of cells with suppressive activity, referred to as MDSCs, may contribute to the negative regulation of immune responses during cancer and other conditions. We previously characterized circulating levels of MDSCs in patients with various types of malignant diseases and reported that increased production of IL-17 correlated with immune suppression involving MDSCs and with malnutrition in patients with gastrointestinal cancers 2,3,14) . VEGF, previously known as vascular permeability factor, is a 45-kDa protein that belongs to a family of platelet-derived growth factors.…”

Glasgow Prognostic Score predicts prognosis of intrahepatic cholangiocarcinoma

“…These may partially underlie the mechanism through which GPS score correlates with the prognosis of ICC patients. Preoperative serum albumin ref lects nutritional status (54,55); it decreases in response to systemic inflammation during malignant tumour growth, leading to hypoalbuminemia and weight loss (56), which may in turn affect the immune system of the cancer patients (57). Hypoalbuminemia therefore suggests systemic inflammation and immune suppression, in association with the initiation and progression of malignant tumours, and has been reported as an independent prognostic marker for ICC (58).…”