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

Shinichi Suzuki; Masahiko Shibata; Kenji Gonda; Yasuyuki Kanke; Mai Ashizawa; Daisuke Ujiie; Seiko Suzushino; Keiichi Nakano; Toshihiko Fukushima; Kenichi Sakurai; Ryouichi Tomita; Kensuke Kumamoto; Seiichi Takenoshita

doi:10.3892/mco.2013.170

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

Mol Clin Oncol. 2013 Nov;1(6):959-964. doi: 10.3892/mco.2013.170. Epub 2013 Aug 22.

Authors

Affiliations

¹ Departments of Thyroid and Endocrinology, Fukushima Medical University, Fukushima 960-1295;
² Tumor and Host Bioscience, Fukushima Medical University, Fukushima 960-1295; ; Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295; ; Department of Gastroenterological Oncology, International Medical Center, Saitama Medical University, Hidaka-shi, Saitama 350-1298;
³ Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295; ; Department of Gastroenterological Oncology, International Medical Center, Saitama Medical University, Hidaka-shi, Saitama 350-1298;
⁴ Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295;
⁵ Department of Surgery, Nihon University School of Medicine, Tokyo 173-8610;
⁶ Department of Surgery, Nippon Dental University, Tokyo 102-8158, Japan.

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.

Keywords: C-reactive protein; anaplastic thyroid carcinoma; hypoalbuminemia; myeloid-derived suppressor cells.