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Myeloid-derived suppressor cells (MDSCs) increase during tumor growth and following cytoreductive therapy resulting in immune dysfunction and tumor escape from host control. We report organ- and tumor-specific expansion of MDSCs, differences in their molecular and membrane phenotypes and T-cell suppressive activity. A significant increase in MDSCs was observed within the spleen, peripheral blood (PB), bone marrow (BM), lungs, and livers of mice bearing orthotopic 4T1, but not CI66 mammary tumors. The PB of 4T1 TB mice had the highest frequency of MDSCs (78.6±2.1%). Similarly, the non-parenchymal cells (NPCs) in the tumor tissue, livers and lungs of 4T1 tumor-bearing (TB) mice had an increased MDSCs frequency. Studies into Gr-1 and Ly-6C staining of MDSCs revealed significant increases in CD11b+Gr-1(dull)Ly-6C(high) and CD11b+Gr-1(bright)Ly-6C(low) subsets. The frequency of MDSCs inversely correlated with the CD3+ T-cell frequency in the spleen, and blood of 4T1 TB mice and was associated with a significant decrease in splenic and NPCs IFN-γ and IL-12 transcript levels, as well as significantly increased levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), interleukin-10 (IL-10), interleukin-13 (IL-13), arginase-1 (ARG-1), nitric oxide synthase (NOS-2), vascular endothelial growth factor-A (VEGF-A) transcripts. In summary, MDSCs are significantly increased not only in lymphoid organs, but also in parenchymal organs including lungs and livers of TB mice, where they may facilitate metastasis to these organ sites., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Products derived from the inner gel of the Aloe vera L. plant have demonstrated multiple clinical activities, and are used routinely to accelerate wound healing. However, typical of natural products, the complex nature of Aloe vera gels may contribute to diverse pharmacologic activities. Our focus on the hematopoietic activities of Aloe vera extracts is extended by these functional studies, which used purified fractions from Aloe vera gel and included a preliminary organ-specific in vitro molecular profile. Studies using a >99% pure carbohydrate fraction from Aloe vera extracts revealed increased hematopoietic and hematologic activity compared to the starting material. In addition, this fraction differentially regulated liver and lung cytokine mRNA levels, resulting in significant increases in message for hematopoietic cytokines [granulocyte colony stimulating factor (G-CSF) and stem cell factor (SCF)]. This profile of activity differed from another fraction obtained from Aloe vera, suggesting the potential for diverse pharmacologic activity. The molecular studies were undertaken using co-cultures of organ slices to limit the amount of purified material required. In summary, these studies revealed significant hematopoietic activity by both pharmacologic and molecular analysis using a >99% pure carbohydrate fraction from Aloe vera gels.