Immunosuppression involving increased myeloid-derived suppressor cell levels, systemic inflammation and hypoalbuminemia are present in patients with anaplastic thyroid cancer

Abstract

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive neoplasms in humans and myeloid-derived suppressor cells (MDSCs) contribute to the negative regulation of immune responses in the context of cancer and inflammation. In order to investigate the pathophysiology of thyroid cancer, peripheral blood mononuclear cells (PBMCs) were obtained from 49 patients with thyroid cancer, 18 patients with non-cancerous thyroid diseases and 22 healthy volunteers. The MDSC levels were found to be higher in patients with any type of thyroid cancer (P<0.05), patients with ATC (P<0.001) and patients with medullary thyroid carcinoma (P<0.05), when compared to patients with non-cancerous thyroid diseases. The MDSC levels were also higher in patients with stage III-IV thyroid cancer compared to those in patients with non-cancerous thyroid diseases (P<0.05). The stimulation index (SI) of phytohemagglutinin (PHA)-induced lymphocyte blastogenesis was significantly lower, the C-reactive protein (CRP) levels were significantly higher and the serum albumin levels were significantly lower in patients with ATC compared to those in patients with non-cancerous thyroid diseases. The SI was significantly lower in stage III and IV thyroid cancer compared to that in non-cancerous thyroid disease (P<0.05). Furthermore, the CRP levels were higher and the concentration of albumin was lower in stage IV thyroid cancer compared to those in non-cancerous thyroid disease (P<0.05). Patients with thyroid carcinoma were then classified into one of two groups according to a %PBMC of MDSC cut-off level of 1.578, which was the average %PBMC of MDSC of patients with any type of thyroid carcinoma. In patients with higher MDSC levels, the production of CRP and interleukin (IL)-10 was significantly higher (P<0.05) and the albumin levels were significantly lower (P<0.05) compared to those in patients with lower MDSC levels. These data indicate that MDSCs are increased in patients with ATC. Furthermore, these patients exhibited suppression of cell-mediated immune responses, chronic inflammation and nutritional impairment.

Circulating Myeloid-Derived Suppressor Cells Predict Differentiated Thyroid Cancer Diagnosis and Extent

“…PTC patients compared with controls, but did show accumulation in patients with anaplastic thyroid cancer (38,39). In contrast, the current study shows significantly higher circulating MDSC levels were observe in a population consisting predominantly of PTC patients.…”

The immune network in thyroid cancer

“…88 Peripheral blood MDSC levels were higher in patients with ATC compared to healthy controls and correlated with the serum level of IL-10, thus suggesting a correlation between MDSCs and systemic immunosuppression. 89 The only study investigating the significance of TC-infiltrating MDSCs failed to find an association between MDSC density and patient survival. 90 Indeed, in a wide cohort of histological samples from 398 TC patients (253 PTCs and 13 FTCs) MDSCs were identified as CD11b C and CD33 C cells.…”

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.…”

“…Kazuo Minamikawa 1) , Masahiko Shibata 1,2) , Kenji Gonda 1) , Daisuke Ujiie 1) , Mai Ashizawa 1) , Takahiro Nakajima 1) , Hirokazu Okayama 1) , Wataru Sakamoto 1) , Motonobu Saito 1) , Tomoyuki Momma 1) , Kousaku Mimura 1,2) , Shinji Ohki 1) , Tatsuo Shimura 3) , Hitoshi Ohto 2) , Seiichi Takenoshita 1,2,3) , Koji Kono 1) E [15][16][17]. The biological significance of the different forms of VEGF has yet to be definitively determined.…”

“…Although a causal relationship between inflammation and the innate immunity in cancerbearing hosts is widely accepted today, the precise cellular mechanisms mediating this relationship have not been elucidated. We have reported several immunological factors, including myeloid-derived suppressor cells (MDSCs), interleukin (IL)-17, and vascular endothelial growth factor (VEGF), in various types of cancer [2][3][4] . IL-17 is a proinflammatory cytokine that is primarily secreted by T helper (Th)17 cells and innate lymphoid cells including γδT cells and natural killer cells 5,6) .…”