The objective of the study was to explore the effects of galectin-9 on myeloid suppressor cells in Coxsackievirus B3 (CVB3)-induced myocarditis and the possible mechanisms involved. For this purpose, BALB/c male mice were infected with CVB3 on day 0 and then received intraperitoneal (IP) administration of recombinant galectin-9 or phosphate-buffered saline (PBS) daily from day 3 to day 7. The phenotypes and functions of myeloid suppressor cells were evaluated. The role and mechanism of myeloid suppressor cells and subsets in CVB3-induced myocarditis in vitro were explored. We found that galectin-9 remarkably increased the frequencies of CD11b+Gr-1+ cells in the cardiac tissue and spleen with myocarditis. Ly-6G+ cells were decreased and Ly-6C+ cells were increased in galectin-9-treated mice. In addition, CD11b+Gr-1+ cells were highly effective in suppressing CD4+ T cells. Moreover, our data demonstrate that CD11b+Gr-1+ cells are capable of expanding regulatory T cells (Tregs) from a preexisting

TY - JOUR. T1 - Myeloid-derived suppressor cells. T2 - Their role in the pathophysiology of hematologic malignancies and potential as therapeutic targets. AU - Younos, Ibrahim H.. AU - Abe, Fuminori. AU - Talmadge, James E.. PY - 2015/8/3. Y1 - 2015/8/3. N2 - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells at various stages of differentiation/maturation that have a role in cancer induction and progression. They function as vasculogenic and immunosuppressive cells, utilizing multiple mechanisms to block both innate and adaptive anti-tumor immunity. Recently, their mechanism of action and clinical importance have been defined, and the cross-talk between myeloid cells and cancer cells has been shown to contribute to tumor induction, progression, metastasis and tolerance. In this review, we focus on the role of MDSCs in hematologic malignancies and the therapeutic approaches targeting MDSCs that are currently in clinical studies.. AB - ...

Tumor-induced, myeloid-derived suppressor cells (MDSCs)-mediated immune system dysfunction can be an essential mechanism leading to tumor immune system escape as well as the inefficacy of cancer immunotherapy. evasion. 0.05; **, 0.01; n.s. = not really significant. Since IL-33 is usually hardly ever secreted by living cells under steady-state circumstances, we gathered tumor supernatant to gauge the secreted IL-33 within tumor microenvironment.17 High degrees of IL-33 were detected in 4T1 tumor supernatant, indicating that IL-33 was also abundantly secreted within tumor cells. However, IL-33 amounts were suprisingly low in the serum of 4T1-bearing mice and undetectable in serum of tumor-free mice (Fig.?1D). After that we decided Rabbit polyclonal to DNMT3A the manifestation of IL-33 receptor C ST2 on MDSCs. Both splenic and tumor MDSCs from 4T1-bearing mice indicated ST2 (Fig.?S1A), interestingly, we discovered that approximately 45% of ST2+ cells in 4T1 cells were also Gr-1+, indicating that ...

The growth and metastasis of solid tumors not only depends on their ability to escape from immune surveillance but also hinges on their ability to invade the vasculature system as well as to induce the formation of new blood vessels. Gr-1(+)CD11b(+) myeloid-derived suppressor cells (MDSCs), overproduced in tumor-bearing hosts, contribute significantly to all these aspects. They also have a potential role in the osteolysis associated with bone metastases. They are formidable partners in tumor metastasis.

article{8578976, abstract = {Solid tumors frequently coexist with a degree of local chronic inflammation. Recruited myeloid cells can therefore be considered as interesting vehicles for tumor-targeted delivery of therapeutic agents. Using in vivo imaging, the short-term accumulation of systemically injected monocytes, macrophages and myeloid-derived suppressor cells (MDSCs) was compared in mice bearing fat pad mammary carcinomas. Monocytes and macrophages demonstrated almost identical in vivo and ex vivo distribution patterns with maximal tumor-associated accumulation seen 48 hours after injection that remained stable over the 4-day follow-up period. However, a substantial accumulation of both cell types was also seen in the liver, spleen and lungs albeit decreasing over time in all three locations. The MDSCs exhibited a similar distribution pattern as the monocytes and macrophages, but demonstrated a better relative on-target fraction over time. Overall, our findings highlight off-target cell ...

Monocytic myeloid-derived suppressor cells (mMDSC) have immunosuppressive properties. Their activity helps the host avoid autoimmune disease but when mMDSC accumulate in a tumor bed, they prevent NK and T cells from eliminating the cancer. We previously found that R848 (a TLR7/8 agonist) reverses this immunosuppression by inducing mMDSC to differentiate into tumoricidal M1 macrophages. To identify the mechanism underlying this effect, we neutralized various cytokines/chemokines in R848 stimulated mMDSC cultures. Blocking IL-6, IL-10, IL-12 and/or TNFα inhibited R848-mediated generation of M1 macrophages. Moreover, combinations of these cytokines induced mMDSC to differentiation more effectively than R848, generating M1 macrophages that efficiently lysed tumor targets. Microarray analysis of the regulatory networks activated following treatment of mMDSC with cytokine combinations or R848 showed that M1 differentiation universally proceeded through a conserved NF-κB, STAT1 and IRF7-dependent ...

In tumor-bearing mice and cancer patients, tumor progression is often associated with altered hematopoiesis leading to the accumulation of myeloid cells. Extensive studies in preclinical models indica

PGE(2) is the key factor needed for MDSCs development, accumulation and functional stability. PGE(2) initiates an EP2/EP4-mediated positive feedback between COX2 and PGE(2) in monocytic precursors, redirecting dendritic cell differentiation to MDSCs. COX2- or EP2/EP4- blockade abrogates MDSC functions and their CXCR4-CXCL12-mediated attraction to cancer environment, providing convenient immunotherapeutic targets ...

Wistar scientists have identified a marker that distinguishes PMN-MDSCs from neutrophils in the blood of patients with a variety of cancers.

Monoclonal antibody against CD11b (Integrin alpha-M, Mac-1 alpha chain), murine expressed by Itgam for use in FACS, Function Blocking, Immunofluorescence, Immunohistochemistry, Immunoprecipitation against Human, Mouse

ITGAM + ITGAX Polyclonal Antibody for Western Blot, Immunofluorescence, Immunocytochemistry, Immunohistochemistry (Paraffin), Flow Cytometry (PA1-46162)

Patients with severe COVID-19 have significantly elevated levels of a certain type of immune cells in their blood, called myeloid-derived suppressor cells. The study may bring an increased understanding of how early immune responses impact disease severity.|br /|

InChI=1S/C29H31N5O3/c1-19-17-23(28-30-20(2)37-32-28)9-11-25(19)21-5-7-22(8-6-21)29(35)31-24-10-12-27(36-4)26(18-24)34-15-13-33(3)14-16-34/h5-12,17-18H,13-16H2,1-4H3,(H,31,35) ...

TY - JOUR. T1 - Derangement of immune responses by myeloid suppressor cells. AU - Serafini, Paolo. AU - De Santo, Carmela. AU - Marigo, Ilaria. AU - Cingarlini, Sara. AU - Dolcetti, Luigi. AU - Gallina, Giovanna. AU - Zanovello, Paola. AU - Bronte, Vincenzo. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2004/2. Y1 - 2004/2. N2 - In tumor-bearing mice and cancer patients, tumor progression is often associated with altered hematopoiesis leading to the accumulation of myeloid cells. Extensive studies in preclinical models indicate that these cells share the CD11b and the Gr-1 markers, possess a mixed mature-immature myeloid phenotype, and are responsible for the induction of T-cell dysfunctions, both tumor-specific and nonspecific. Moreover, CD11b+ Gr-1+ myeloid cells are described under different unrelated situations associated with temporary impairment of the T-lymphocyte reactivity. This review examines recent findings on the nature, properties, and mechanisms of ...

TY - JOUR. T1 - Myeloid-derived suppressor cells. T2 - Cellular missiles to target tumors. AU - Chandra, Dinesh. AU - Gravekamp, Claudia. PY - 2013. Y1 - 2013. N2 - While conventional anticancer therapies, including surgical resection, radiotherapy, and/or chemotherapy, are relatively efficient at eliminating primary tumors, these treatment modalities are largely ineffective against metastases. At least in part, this reflects the rather inefficient delivery of conventional anticancer agents to metastatic lesions. We have recently demonstrated that myeloid-derived suppressor cells (MDSCs) can be used as cellular missiles to selectively deliver a radioisotope-coupled attenuated variant of Listeria monocytogenes to both primary and metastatic neoplastic lesions in mice with pancreatic cancer. This novel immunotherapeutic intervention robustly inhibited tumor growth while promoting a dramatic decrease in the number of metastases.. AB - While conventional anticancer therapies, including surgical ...

Myeloid-derived suppressor cells (MDSCs) are derived from myeloid progenitor cells present in the bone marrow. When the differentiation of the myeloid progenito...

Increasing evidence supports the multifaceted effect of tumor-produced prostanoids on cancer progression. PGE2 not only enhances tumorigenesis by conferring a metastatic phenotype, increasing resistance to apoptosis and stimulating angiogenesis, it also impairs the host immune response. PGE2 has been shown to decrease IL-12 and increase IL-10 production in dendritic cells and macrophages (24-26). PGE2 may also influence a wide range of T cell functions, including inhibition of T lymphocyte activation and proliferation (27), promoting the development of a Th2 response and inhibiting the production of the Th1 cytokines IL-2 and interferon γ (28). PGE2 produced by macrophages may also decrease proliferation and inhibit T cell cytotoxic responses (29, 30). However, macrophage-derived PGE2 is not playing a role in the induction of arginase I, because the injection of 3LL in COX-2 knockout mice was similar to wild-type mice bearing tumors. The multiplicity of effects caused by PGE2 may be explained ...

In recent years, bone marrow-derived immature and mature myeloid cells have been extensively investigated, as they are endowed with a high capability to exert protumor functions (Gabrilovich et al., 2012). Indeed, these cells can suppress antigen-specific immune responses (immature myeloid cells or myeloid-derived suppressor cells), exert a proangiogenic activity (immature myeloid cells or neutrophils; Murdoch et al., 2008; Motz and Coukos, 2011), or induce chemoresistance and invasion or metastasis (immature myeloid cells; Yang et al., 2008; Acharyya et al., 2012). These cells are recruited to tumor microenvironment mainly by chemokines constitutively released by tumor and stromal cells (Mantovani et al., 2010; Qian et al., 2011; Acharyya et al., 2012) or produced after some aggressive treatments (Kerbel, 2008). Our study highlights an unanticipated role of tumor-derived oxysterols/LXR ligands, which contribute to the recruitment of protumor neutrophils in a CXCR2-dependent manner, ultimately ...

In cancer, infection and inflammation, the immune systems function can be dysregulated. Instead of fighting disease, immune cells may increase pathology and suppress host-protective immune responses. Myeloid cells show high plasticity and adapt to changing conditions and pathological challenges. De …

Mouse monoclonal antibody raised against native ITGAM. Native purified ITGAM from rheumatoid synovial cells and human monocytes. (MAB6032) - Products - Abnova

Suppression of immune responses has been described in situations as disparate as tumor growth, graft-vs-host disease, infection with recombinant vaccines and parasites, and treatment with cyclophosphamide and superantigens. The common feature in all these conditions is the recruitment of Gr-1+CD11b+ myeloid cells to secondary lymphoid organs. Depletion and add-back experiments have demonstrated that in these situations, the Gr-1+CD11b+ myeloid cells are both necessary and sufficient for suppression of T and B cell responses. Previous studies using bulk populations of MSC have provided insights into the immunosuppressive process but have not defined the properties of a single, well-defined cell type. In the current paper we have used cloned MSC lines (27) to examine the immunosuppressive mechanisms used by homogeneous populations of suppressor cells.. It is noteworthy that the cloned MSC are extremely potent inhibitors of T cell proliferation, but that inhibition, at least for the first 24 h, is ...

The researchers examined the patients peripheral blood immune profiles at baseline and after two and four treatment cycles, with CD3, CD4, CD8, NK (CD56), Treg (FOXP3), and myeloid-derived suppressor cell lymphocyte subpopulations assessed by using fluorescence-activated cell sorting analysis.The results showed that after treatment with nivolumab, 20 patients had a complete or partial response or stable disease, while 34 had progressive disease ...

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The tumor microenvironment is a complex milieu of tumor and host cells. Host cells can include tumor-reactive T cells capable of killing tumor cells. However, more frequently the tumor and host components interact to generate a highly immune suppressive environment that frustrates T cell cytotoxicity and promotes tumor progression through a variety of immune and non-immune mechanisms. Myeloid-derived suppressor cells (MDSC) are a major host component contributing to the immune suppressive environment. In addition to their inherent immune suppressive function, MDSC amplify the immune suppressive activity of macrophages and dendritic cells via cross-talk. This article will review the cell-cell interactions used by MDSC to inhibit anti-tumor immunity and promote progression, and the role of inflammation in promoting cross-talk between MDSC and other cells in the tumor microenvironment.

The monocyte phagocyte system (MPS) includes numerous monocyte, macrophage, and dendritic cell (DC) populations that are heterogeneous, both phenotypically and functionally. In this study, we sought to characterize those diverse MPS phenotypes with mass cytometry (CyTOF). To identify a deep phenotype of monocytes, macrophages, and DCs, a panel was designed to measure 38 identity, activation, and polarization markers, including CD14, CD16, HLA-DR, CD163, CD206, CD33, CD36, CD32, CD64, CD13, CD11b, CD11c, CD86, and CD274. MPS diversity was characterized for 1) circulating monocytes from healthy donors, 2) monocyte-derived macrophages further polarized in vitro (i.e., M-CSF, GM-CSF, IL-4, IL-10, IFN-γ, or LPS long-term stimulations), 3) monocyte-derived DCs, and 4) myeloid-derived suppressor cells (MDSCs), generated in vitro from bone marrow and/or peripheral blood. Known monocyte subsets were detected in peripheral blood to validate the panel and analysis pipeline. Then, using various culture conditions

The Myeloid-Derived Suppressor Cell Isolation Kit has been developed for the isolation of Gr-1highLy-6G+ and Gr-1dimLy-6G- myeloid cells from lymphoid tissue. This Kit works ideally for spleen and tumor tissues. | Canada

title: Role of myeloid-derived suppressor cells in mouse pre-sensitized cardiac transplant model., doi: 10.1016/j.clim.2014.03.013, category: Article

TAMPA, Fla. - Researchers at the Moffitt Cancer Center have found a potential mechanism by which immune suppressive myeloid-derived suppressor cells can prevent immune response from developing in cancer. This mechanism includes silencing the tumor suppressor gene retinoblastoma 1 or Rb1. Their data explains a new regulatory mechanism by which myeloid-derived suppressor cells are expanded in cancer.. Their study appeared in a recent issue of Nature Immunology.. According to the authors, two kinds of myeloid-derived suppressor cells - monocytic M-MDSCs and granulocytic PMN-MDSCs - regulate immune responses in cancer and other conditions. In experiments with tumor-bearing mice, they discovered that M-MDSCs acquire some of the physical characteristics of PMN-MDSCs. Acquisition of the PMN-MDSCs characteristics, they found, was mediated by the silencing of Rb1 by modifications in a histone deacetylase 2 (HDAC-2), an enzyme decoded by the HDAC2 gene.. Our findings demonstrate the function of a newly ...

The molecular chaperone alphaB-crystallin has emerged as a target for cancer therapy due to its expression in human tumors and its role in regulating tumor angiogenesis. alphaB-crystallin also reduces neuroinflammation, but its role in other inflammatory conditions has not been investigated. Here, we examined whether alphaB-crystallin regulates inflammation associated with tumors and ischemia. We found that CD45(+) leukocyte infiltration is 3-fold increased in tumors and ischemic myocardium in alphaB-crystallin-deficient mice. Notably, alphaB-crystallin is prominently expressed in CD11b(+) Gr-1(+) immature myeloid cells (IMCs), known as regulators of angiogenesis and immune responses, while lymphocytes and mature granulocytes show low alphaB-crystallin expression. alphaB-Crystallin deficiency results in a 3-fold higher accumulation of CD11b(+) Gr-1(+) IMCs in tumors and a significant rise in CD11b(+) Gr-1(+) IMCs in spleen and bone marrow. Similarly, we noted a 2-fold increase in CD11b(+) ...

Inflammation plays a critical role in the development of severe neonatal morbidities. Myeloid-derived suppressor cells (MDSCs) were recently implicated in the regulation of immune responses in newborns. Here, we report that the presence of MDSCs and their functional activity in infants are closely associated with the maturity of newborns and the presence of lactoferrin (LF) in serum. Low amounts of MDSCs at birth predicted the development of severe pathology in preterm infants - necrotizing enterocolitis (NEC). In vitro treatment of newborn neutrophils and monocytes with LF converted these cells to MDSCs via the LRP2 receptor and activation of the NF-κB transcription factor. Decrease in the expression of LRP2 was responsible for the loss of sensitivity of adult myeloid cells to LF. LF-induced MDSCs (LF-MDSCs) were effective in the treatment of newborn mice with NEC, acting by blocking inflammation, resulting in increased survival. LF-MDSCs were more effective than treatment with LF protein ...

Inflammation plays a critical role in the development of severe neonatal morbidities. Myeloid-derived suppressor cells (MDSCs) were recently implicated in the regulation of immune responses in newborns. Here, we report that the presence of MDSCs and their functional activity in infants are closely associated with the maturity of newborns and the presence of lactoferrin (LF) in serum. Low amounts of MDSCs at birth predicted the development of severe pathology in preterm infants - necrotizing enterocolitis (NEC). In vitro treatment of newborn neutrophils and monocytes with LF converted these cells to MDSCs via the LRP2 receptor and activation of the NF-κB transcription factor. Decrease in the expression of LRP2 was responsible for the loss of sensitivity of adult myeloid cells to LF. LF-induced MDSCs (LF-MDSCs) were effective in the treatment of newborn mice with NEC, acting by blocking inflammation, resulting in increased survival. LF-MDSCs were more effective than treatment with LF protein ...

Inflammation plays a critical role in the development of severe neonatal morbidities. Myeloid-derived suppressor cells (MDSCs) were recently implicated in the regulation of immune responses in newborns. Here, we report that the presence of MDSCs and their functional activity in infants are closely associated with the maturity of newborns and the presence of lactoferrin (LF) in serum. Low amounts of MDSCs at birth predicted the development of severe pathology in preterm infants - necrotizing enterocolitis (NEC). In vitro treatment of newborn neutrophils and monocytes with LF converted these cells to MDSCs via the LRP2 receptor and activation of the NF-κB transcription factor. Decrease in the expression of LRP2 was responsible for the loss of sensitivity of adult myeloid cells to LF. LF-induced MDSCs (LF-MDSCs) were effective in the treatment of newborn mice with NEC, acting by blocking inflammation, resulting in increased survival. LF-MDSCs were more effective than treatment with LF protein ...

There has been a great deal of interest in the immunostimulatory properties of GM-CSF in autoimmune diseases and for immunotherapy in cancer (29, 30). More than 15 years ago, Dranoff and colleagues showed that GM-CSF, in the context of γ-irradiated tumor cells, elicits potent immune responses in a murine model of melanoma (22). This prompted the study of GM-CSF as an adjuvant to whole tumor, DNA, and peptide vaccination with promising results in a number of animal tumor models (23, 31-34). Similar strategies were safely carried out in early phase clinical trials and immune responses were elicited (35-38). However, in more recent randomized clinical trials, GM-CSF was found to have detrimental effects on both immune responses and clinical outcomes (5-7), a finding that may be related to the expansion of MDSCs. Several groups have observed that GM-CSF dose and duration of exposure may mediate MDSC expansion (16, 28, 39-42). However, a direct connection between MDSC expansion and the failings of ...

MDSC are important mediators of tumor-induced immunosuppression in pancreatic cancer. Inhibiting MDSC accumulation with zoledronic acid improves the host anti-tumor response in animal studies suggesting that efforts to block MDSC may represent a novel treatment strategy for pancreatic cancer.

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Mice and treatments. BALB-neuT mice were bred and maintained in the animal facility at the Istituto Nazionale Tumori, according to the national and institutional guidelines. Normal 8 to 10-week-old BALB/c, C57BL/6, and FVB mice were purchased from Charles River. F1 hybrids were obtained by mating BALB-neuT males with C57BL/6 or FVB females. The hemizygous transgenic females were identified by PCR performed at age 3 weeks ( 24).. MMP-9+/− mice on C57BL/6 background were kindly provided by Dr. Leif Lund (Panum Institute, Department of Experimental Medicine, University of Copenhagen, Copenhagen, Denmark) as N17 generation. They were backcrossed to BALB/c and the N6 generation, intercrossed to obtain either homozygous MMP-9−/− and heterozygous MMP-9+/− offspring to be used as bone marrow donors.. Zoledronate (Zometa; Novartis Europharm, Ltd.) at a dose of 0.1 mg/kg or pamidronate (Faulding Pharmaceuticals) at a dose of 2 mg/kg were diluted in saline and administered daily s.c. 5 days a week. ...

Mouse monoclonal antibody raised against human ITGAM. Dendritic cells derived from human monocytes. (MAB13801) - Products - Abnova

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B lymphopoiesis declines with age, and this decline correlates with increased adipose tissue in the bone marrow (BM). Also, adipocyte-derived factors are known to inhibit B lymphopoiesis. Using cocultures of mouse BM cells with OP9 stromal cells, we found that adipocyte-conditioned medium induces the generation of CD11b+Gr1+ myeloid cells, which inhibit B cell development in vitro. Adipocyte-conditioned medium-induced CD11b+Gr1+ cells express Arg1 (arginase) and Nos2 (inducible NO synthase) and suppress CD4+ T cell proliferation, indicating that these cells are myeloid-derived suppressor cells (MDSCs). Blocking arginase and inducible NO synthase did not restore B lymphopoiesis, indicating that inhibition is not mediated by these molecules. Transwell and conditioned-medium experiments showed that MDSCs inhibit B lymphopoiesis via soluble factors, and by cytokine array we identified IL-1 as an important factor. Addition of anti-IL-1 Abs restored B lymphopoiesis in BM cultures containing MDSCs, ...

UNRAVELING MECHANISMS UNDERLYING MYELOID-DERIVED SUPPRESSOR CELL ORCHESTRATION OF OVARIAN CANCER PROGRESSION A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Microbiology and Immunology by Kevin Matthew Hart DARTMOUTH COLLEGE Hanover, New Hampshire June 14th, 2011 Examining Committee: ____________________________ (Chair) Brent Berwin, Ph.D. ____________________________ James Gorham, M.D., Ph.D. ____________________________ Mary Jo Turk, Ph.D. ____________________________ ____________________________ James Talmadge, Ph.D. Brian W. Pogue, Ph.D. Dean of Graduate Studies ...

Background: Lupus erythematosus (LE) is a heterogeneous disease ranging from mainly skin-restricted manifestations (discoid LE [DLE] and subacute cutaneous LE) to a progressive multisystem disease (systemic LE [SLE]). Genetic association studies have recently identified several strong susceptibility genes for SLE, including integrin alpha M (ITGAM), also known as CD11b, whereas the genetic background of DLE is less clear. Principal Findings: To specifically investigate whether ITGAM is a susceptibility gene not only for SLE, but also for cutaneous DLE, we genotyped 177 patients with DLE, 85 patients with sporadic SLE, 190 index cases from SLE families and 395 population control individuals from Finland for nine genetic markers at the ITGAM locus. SLE patients were further subdivided by the presence or absence of discoid rash and renal involvement. In addition, 235 Finnish and Swedish patients positive for Ro/SSA-autoantibodies were included in a subphenotype analysis. Analysis of the ITGAM ...

article{7a1531c6-a64d-4441-8d85-f0b777c798d3, abstract = {We were the first to demonstrate that combined immunotherapy with GM-CSF producing GL261 cells and recombinant IFNgamma of preestablished GL261 gliomas could cure 90% of immunized mice. To extend these findings and to uncover the underlying mechanisms, the ensuing experiments were undertaken. We hypothesized that immunizations combining both GM-CSF and IFNgamma systemically would increase the number of immature myeloid cells, which then would mature and differentiate into dendritic cells (DCs) and macrophages, thereby augmenting tumor antigen presentation and T-cell activation. Indeed, the combined therapy induced a systemic increase of both immature and mature myeloid cells but also an increase in T regulatory cells (T-regs). Cytotoxic anti-tumor responses, mirrored by an increase in Granzyme B-positive cells as well as IFNgamma-producing T-cells, were augmented after immunizations with GM-CSF and IFNgamma. We also show that the combined ...

In this study, we evaluated the nature of tumor-associated MDSC by comparing the phenotype and function of MDSC isolated from spleen and tumor sites from the same mice. It is known that MDSC can differentiate into MΦ and DC (Kusmartsev and Gabrilovich, 2003, 2005). Therefore, it was important to assure that we are indeed comparing cells with the same phenotype. We sorted MDSC based on the expression of Gr-1 and CD11b, two markers which are considered hallmarks of MDSC. MDSCs from the tumor site and spleen had similar morphology and phenotype. Expression of the macrophage cell marker F4/80 was slightly higher on tumor MDSC than on spleen cells. However, such rather minor phenotypic differences contrasted with profound differences in MDSC function. As was reported previously (Corzo et al., 2009), spleen MDSC contain a high level of ROS and a relatively modest level of NO and arginase I activity (although it was still elevated in comparison with Gr-1+CD11b+ cells from naive mice). In striking ...

Fig. 3 Cell morphology can be linked to transcriptional states.. (A) Representative images from RNA FISH analysis of THP-1 macrophages treated with LPS (100 ng/ml) for IL1B (red) and NR3C1 (green) transcripts, as described in Materials and Methods. Bottom: Merged image of fluorescence channels and differential interference contrast images. (B) Quantification of cell size (arbitrary units) and eccentricity (0 = circle, 1 = ellipse) for cells with high expression of the indicated genes, as described in Materials and Methods. N indicates the number of cells analyzed. Data were acquired from two independent experiments. The red box plots represent data from IL1B-positive cells. White box plots represent data from cells with high expression (top 50%) of the genes indicated at the top of the panel. Statistical analysis was done by one-way ANOVA followed by Dunns multiple comparisons test. **P , 0.01; ***P , 0.001. a.u., arbitrary units; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; n.s., not ...

Purpose: Before metastasis, primary tumor can create a premetastatic niche in distant organ to facilitate the dissemination of tumor cells. In the premetastatic phase, the permeability of pulmonary vasculatures is increased to accelerate the extravasation of circulating tumor cells. However, it is not clear whether local miRNAs contribute to the vascular hyperpermeability of the premetastatic niche. Experimental Design: The expression of total miRNAs was determined using microarray in series of premetastatic lungs from tumor-bearing mice. Significantly differentially expressed miRNAs were identified and validated with qRT-PCR. Vascular permeability assays, vascular mimic systems, and orthotopic tumor models were used to investigate roles of selected miRNAs and target genes in premetastatic hyperpermeability. Results: We identified a miRNA signature in premetastatic lungs. Among these miRNAs, miR-30a, b, c, d and e were significantly attenuated. Subsequent investigations elucidated that lung ...

Multiple tumor-derived factors are responsible for the accumulation and expansion of immune suppressing myeloid-derived suppressor cells (MDSCs) and M2-like tumor-associated macrophages (TAMs) in tumors. Here we show that treatment of tumor-bearing mice with docetaxel in combination with the phosphatidylserine (PS)-targeting antibody, 2aG4, potently suppressed the growth and progression of prostate tumors, and depleted M2-like TAMs and MDSCs and increased the presence of M1-like TAMs and mature dendritic cells in the tumors. In addition, the antibody markedly altered the cytokine balance in the tumor microenvironment from immunosuppressive to immunostimulatory. In vitro studies confirmed that 2aG4 re-polarized TAMs from an M2 to M1-like phenotype and drove MDSCs differentiating into M1-like TAMs and functional dendritic cells. These data suggest that PS is primarily responsible for expansion of MDSCs and M2-like TAMs in tumors, and that bavituximab, a PS-targeting antibody currently in cancer ...

Perform reliable qPCR with Bio-Rads pre-validated ITGAM primer pair, for the Dog genome. Designed for SYBR Green-based detection.

Perform reliable qPCR with Bio-Rads pre-validated Itgam primer pair, for the Mouse genome. Designed for SYBR Green-based detection.

Thymosin α1 (Tα1) has been tested for cancer therapy for several years, in most cases, the anti-tumor effect of Tα1 was limited, especially when Tα1 was used as a single agent. The role of Tα1 in cancer treatment and the regulatory mechanisms by which Ta1 takes effects are not yet completely understood. Using a Lewis lung caner model, here we report that Tα1 used alone elevated CD8(+) T cells, but failed to inhibit tumor growth. Furthermore, immunosuppressive myeloid-derived suppressor cells (MDSCs) showed heightened Arginase 1 production in response to Tα1 treatment, which led to stronger suppression of anti-tumor immunity ...

Myeloid-derived suppressor cells (MDSC) certainly are a main element of the immune system suppressive network defined in cancer and several additional pathological conditions. tumor-free mice. Manifestation of NOX2 subunits in MDSC was managed by the STAT3 transcription element. In the lack of NOX2 activity MDSC dropped the capability to suppress T-cell reactions and quickly differentiated Read More. ...