Abstract. Circulating cluster of differentiation (CD)14+ human leukocyte antigen (HLA)-DRlow/- monocytes, those with a lower HLA-DR expression or are negative for HLA-DR, are considered to be involved in systemic immunosuppression

Circulating cluster of differentiation (CD)14+ human leukocyte antigen (HLA)-DRlow/monocytes, those with a lower HLA-DR expression or are negative for HLA-DR, are considered to be involved in systemic immunosuppression in patients with several malignant tumors. However, few studies have investigated in detail the gene expression profile of CD14+HLA-DRlow/monocytes. In the present study, the mRNA expression levels of immune-associated molecules in CD14+ monocytes isolated from healthy donors and patients with renal cell carcinoma (RCC) were analyzed. Consistent with previous studies, the percentage of HLA-DRlow/cells in CD14+ monocytes was significantly increased in patients with RCC compared with healthy donors. In 3 of the 4 patients who underwent surgical resection of the primary tumor, the percentage of CD14+HLA-DRlow/cells was significantly decreased following surgery. The mRNA expression levels of cyclooxygenase 2, transforming growth factor β, interleukin 6R, chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-X-C motif) ligand 10 (CXCL10), oncostatin M, and vascular endothelial growth factor-A in CD14+ monocytes were quantified using reverse transcription‐quantitative polymerase chain reaction. The results of the present study revealed that increased expression levels of CCL2 and CXCL10 were inversely correlated with the percentage of CD14+HLA-DRlow/monocytes. This suggested that monocytes in RCC patients were immunologically suppressed, and that immunosuppression in RCC patients may be due, in part, to the dysfunction of circulating monocytes. Introduction Systemic immunosuppression in cancer patients is considered to affect the progression of cancer, and therefore the treatment outcome (1,2). Renal cell carcinoma (RCC) is known to be resistant to conventional chemotherapeutic agents and is known to induce an immunosuppressive environment. Although tyrosine kinase inhibitors (TKIs), including sorafenib and sunitinib, are widely utilized for the treatment of patients with metastatic RCC and TKIs are expected to act as adjuvants for immunotherapeutic effects (3,4), the anticancer effects of TKIs may be unable to overcome the immunosuppressive microenvironment of RCC hosts (5). Previous studies have indicated that myeloid lineage cells, including tumor‐associated macrophages, inflammatory monocytes and myeloid-derived suppressor cells (MDSCs), have a significant role in cancer‐induced immunosuppression (6,7). MDSCs were initially described in murine cancer models. However, it remains to be elucidated which cell populations in humans are comparable to murine MDSCs (6). Several studies have revealed that cancer patients exhibit an increase in the number of cluster of differentiation (CD)14+ human leukocyte antigen (HLA)-DRlow/cells, those with a lower HLA-DR expression or are negative for HLA-DR, circulating in the blood (8-10). CD14+HLA-DRlow/cells that were isolated from cancer patients were identified to suppress T‐cell activation in culture, and thus these CD14+HLA-DRlow/monocyte populations were considered to act as MDSCs (6,8-10). In the present study, in order to investigate the immunological characteristics of human monocyte populations, HLA-DR and the gene expression of immune-associated molecules in circulating CD14+ myeloid cells from RCC patients were evaluated. Materials and methods Blood samples. The protocol of the present study was approved by the Kumamoto University Review Board (ethical permit no. 509; Kumamoto University Hospital, Kumamoto, Japan). All healthy donors and patients reviewed the study objectives CXCL10 and CCL2 mRNA expression in monocytes is inversely correlated with the HLA‐DR lower fraction of monocytes in patients with renal cell carcinoma TAKANOBU MOTOSHIMA1,2, YOSHIHIRO KOMOHARA2, HASITA HORLAD2, HIROTAKE TSUKAMOTO3, MITSUGU FUJITA4, YOICHI SAITO2, KENICHIRO TANOUE1, YUTAKA KASEJIMA1, YUTAKA SUGIYAMA1, YOSHIAKI KAWANO1, YASUHARU NISHIMURA3, MOTOHIRO TAKEYA2 and MASATOSHI ETO1 Departments of 1Urology, 2Cell Pathology and 3Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556; 4Department of Microbiology, Kinki University Faculty of Medicine, Osaka 542‐0073, Japan Received December 3, 2014; Accepted December 18, 2015 DOI: 10.3892/ol.2016. 4132 Correspondence to: Dr Yoshihiro Komohara, Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan E-mail: ycomo@kumamoto-u.ac. jp