Abstract 5416: Myeloid-derived suppressor cells (MDSC) are increased and correlated with immune suppression and chronic inflammation in patients with cancer

Abstract

Abstract Chronic inflammation plays a key role in the progress of malignant diseases and has been reported to relate with immune suppression seen in patients with advanced diseases. MDSC: myeloid-derived suppressor cells found as a new type of immune suppressor cells are enhanced by inflammation and have been reported to be present in blood circulation, lymphnodes and tumor tissues in patients with cancer. The suppression of immune function via depleting arginine and producing immune-suppressing cytokines including IL-10 has also been reported. In order to investigate MDSC in patients, peripheral blood mononuclear cells (PBMC) were collected from 18 normal healthy volunteers, 53 patients with gastrointestinal cancer, 65 with breast cancer, 8 with thyroid cancer, and 5 with ovarian cancer. These cells were used for the detection of MDSC (CD11b+CD14−CD33+) by flow cytometry. PBMC was also used for the PHA-blastogenesis of lymphocytes which is a marker of cell mediated immunity (stimulation indices: SI) and for the production assay of cytokines including IL-6 and IL-10. MDSC (%PBMC) of whole patients (5.68 + 5.92%), those of gastrointestinal cancer patients (3.76 + 4.90%) and those of breast cancer patients (2.92 + 4.13%) were significantly higher than those of normal volunteers (p<0.005, p=0.05, p<0.05, respectively, vs 1.59 + 1.08%). MDSC were inversely correlated with the SI (r=−0.271, p<0.05) in patients with gastrointestinal cancer and positively correlated with IL-6 production in whole patients(r=0.287, p=0.05) and with IL-10 production in patients with breast cancer (r=0.363, p<0.05). They were also significantly correlated to neutrophil counts (r=0.287, p<0.05) and neutrophil/lymphocyte ratios (NLR, r=0.623, p=0.05), and inversely correlated to lymphocyte counts (r=−0.251, p<0.01). Thus MDSC were successfully detected in peripheral blood and were significantly higher in patients with cancer. There were strong relationships among the inhibition of cell-mediated immunity, production of type 2 cytokines and inflammatory markers such as NLR. Therefore, MDSC seemed to work as a suppressor of immune reaction and may be an important marker of chronic inflammation in patients with cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5416. doi:1538-7445.AM2012-5416