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Evaluation of immune dysfunction during the tumor-bearing state is a critical issue in combating cancer. In this study, we initially found that IL-6, one of the cachectic factors, suppressed CD4+ T cell-mediated immunity through downregulation of MHC class II by enhanced arginase activity of dendritic cells (DC) in tumor-bearing mice. We demonstrated that administration of Ab against IL-6R (anti-IL-6R mAb) greatly enhanced T cell responses and inhibited the growth of tumor in vivo. We also found that IL-6 upregulated the expression of arginase-1 and arginase activity of DC in vitro. Tumor-infiltrating CDllc+ DC exhibited upregu-lated mRNA expression of arginase-1 but reduced expression of MHC class II in parallel with the increase in serum IL-6 levels at the late stage in tumor-bearing hosts. However, the administration of anti-IL-6R mAb into tumor-bearing mice inhibited both the downmodulation of MHC class II and the upregulation of arginase-1 mRNA levels in DC. Furthermore, we noted that Nω-hydroxy-L-arginine or L-arginine, an arginase-1 inhibitor, blocked the reduction in MHC class II levels on CDllc+ DC during the tumor-bearing state. Finally, we demonstrated that the administration of Nω-hydroxy-L-arginine at the peritumor site significantly enhanced CD4+ T cell responses and inhibited tumor growth. Thus, IL-6-mediated arginase activation and the subsequent reduc-tion in MHC class II expression on DC appeared to be critical mechanisms for inducing dysfunction of the immune system in the tumor-bearing state. Blockade of the IL-6-arginase cascade is a promising tool to overcome the dysfunction of antitumor immunity in tumor-bearing hosts. [ABSTRACT FROM AUTHOR]

Background: The neutrophil:lymphocyte ratio (NLR) has been reported to reflect systemic inflammation and to have independent prognostic value for patients with various cancers. In this study, we analyzed the association between NLR and clinicopathological factors and verified the significance of NLR as a prognostic factor for Japanese patients with breast cancer., Patients and Methods: A total of 167 Japanese female patients with stage I-III breast cancer were retrospectively recruited into this study. Associations with clinicopathological factors and NLR were assessed, and disease-free survival and breast cancer-specific survival were estimated., Results: In multivariate analysis, lymph node metastases and NLR were significantly associated with disease-free survival and breast cancer-specific survival. NLR was significantly higher in patients with lower body-mass index., Conclusion: Preoperative NLR may be an independent prognostic factor for survival in Japanese patients with breast cancer. Reduction of body mass index has been implicated in NLR elevation, particularly in postmenopausal women., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Androgen receptors (ARs) are expressed in many breast cancer cells, but the mechanism of action of androgens is not as well-characterized as in other cell types. The study of microRNAs has recently provided with important insights into the biology of hormone-dependent cancer., Materials and Methods: We attempted to identify microRNAs induced by dihydrotestosterone in an AR-positive cell line. We examined a possible correlation among microRNAs, target genes, and ARs in breast cancer tissues using immunohistochemistry and laser capture microscopy., Results: Our analysis demonstrated that miR-363 and its possible target IQ motif and WD repeats-1 (IQWD1) are involved in a microRNA-mRNA pathway related to the mechanism of action of androgens. Our analyses showed that a high tumor level of IQWD1 in patients with breast cancer was significantly associated with adverse clinical outcomes., Conclusion: Our findings indicated that the recruitment of IQWD1 to ARs may be a prerequisite for the growth stimulation by androgens through ARs in breast cancer cells.