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Mark Bloomston - One of the best experts on this subject based on the ideXlab platform.

  • distinct myeloid suppressor cell subsets correlate with plasma il 6 and il 10 and reduced interferon alpha signaling in cd4 t cells from patients with gi malignancy
    Cancer Immunology Immunotherapy, 2011
    Co-Authors: Gregory S Young, Todd M Bauer, Elaine Binkley, Mark Bloomston, Bethany L Mundybosse
    Abstract:

    Interferon-alpha (IFN-α) promotes anti-tumor immunity through its actions on immune cells. We hypothesized that elevated percentages of myeloid-derived suppressor cells (MDSC) and increased pro-inflammatory cytokines in peripheral blood would be associated with impaired response to IFN-α in patients with gastrointestinal (GI) malignancies. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets, and IFN-α-induced signal transduction in 40 patients with GI malignancies. Plasma IL-6 and IL-10 were significantly higher in patients versus normal donors. CD33+HLADR−CD11b+CD15+ and CD33+HLADR−/lowCD14+ MDSC subsets were also elevated in patients versus normal donors (P < 0.0001). Plasma IL-6 was correlated with CD33+HLADR−CD15+ MDSC (P = 0.008) and IL-10 with CD33+HLADR−CD15− MDSC (P = 0.002). The percentage of CD15+ and CD15− but not CD14+ MDSC subsets were inversely correlated with IFN-α-induced STAT1 phosphorylation in CD4+ T cells, while co-culture with in vitro generated MDSC led to reduced IFN-α responsiveness in both PBMC and the CD4+ subset of T cells from normal donors. Exploratory multivariable Cox proportional hazards models revealed that an increased percentage of the CD33+HLADR−CD15− MDSC subset was associated with reduced overall survival (P = 0.049), while an increased percentage of the CD33+HLADR−/lowCD14+ subset was associated with greater overall survival (P = 0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets, and IFN-α responsiveness in patients with GI malignancies.

  • abstract 5517 distinct myeloid suppressor cell subsets correlate with plasma il 6 and il 10 and reduced interferon α signal transduction in cd4 t cells from patients with gastrointestinal malignancy
    Cancer Research, 2011
    Co-Authors: Bethany L Mundy, Gregory S Young, Todd M Bauer, Elaine Binkley, Mark Bloomston, Matthew A Bill, Tanios Bekaiisaab, William E Carson, Gregory B Lesinski
    Abstract:

    Interferon-alpha (IFNα) can promote anti-tumor immunity through its actions on immune cells. We have shown in murine models that a class of immune suppressor cells known as myeloid-derived suppressor cells (MDSC) have inhibitory effects on IFN signal transduction and gene regulation. Interleukin (IL)-6 and IL-10 are produced by tumor cells in cancer patients and can regulate the survival and function of MDSC. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets and IFNα-induced signal transduction in 40 patients with gastrointestinal (GI) malignancies. Plasma IL-6 and IL-10 levels were significantly higher in patients versus normal donors. CD33 + HLADR − CD11b + CD15 + and CD33 + HLADR −/low CD14 + MDSC were also elevated in patients versus normal donors (p + ) and monocytic (CD15 − ) subsets. Therefore relationships between CD15 expression on MDSC and cytokines elevated in GI patients were examined. A significant correlation between plasma IL-6 with CD33 + HLADRCD15 + MDSC (p=0.008) and IL10 with CD33 + HLADR − CD15 − MDSC (p=0.002) was observed. The level of CD15 + and CD15 − but not CD14 + MDSC subsets were inversely correlated with IFNα-induced STAT1 phosphorylation in CD4 + T cells, while co-culture with in vitro generated MDSC led to reduced IFNα-responsiveness in PBMC from normal donors. In a multivariable Cox proportional hazards model, an increased percentage of the CD33 + HLADR − CD15 − MDSC subset was associated with reduced overall survival (hazard ratio = 1.43; p = 0.049) while an increased percentage of the CD33 + HLADR −/low CD14 + subset was associated with greater overall survival (hazard ratio = 0.69, p=0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets and IFNα responsiveness in patients with GI malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5517. doi:10.1158/1538-7445.AM2011-5517

Gosse J Adema - One of the best experts on this subject based on the ideXlab platform.

  • increase in both CD14 positive and cd15 positive myeloid derived suppressor cell subpopulations in the blood of patients with glioma but predominance of cd15 positive myeloid derived suppressor cells in glioma tissue
    Journal of Neuropathology and Experimental Neurology, 2015
    Co-Authors: Paul R Gielen, Barbara M Schulte, Esther D Kersrebel, Kiek Verrijp, Harriette M J M Petersenbaltussen, Mark Ter Laan, Pieter Wesseling, Gosse J Adema
    Abstract:

    Myeloid-derived suppressor cells (MDSCs), defined as CD33-positive major histocompatibility complex class II-negative cells, are increased in a variety of human tumors and are associated with immunosuppression. Myeloid-derived suppressor cells can be further subdivided into CD14-positive monocytic MDSC and CD15-positive granulocytic MDSC (polymorphonuclear MDSC) subpopulations. Here we analyzed MDSC subsets in the blood and tumor tissue of patients with glioma, including the most malignant variant, glioblastoma multiforme (GBM). CD33-positive major histocompatibility complex class II-negative MDSCs in blood from 21 patients with glioma and 12 healthy individuals were phenotyped and quantified by flow cytometry. Myeloid populations of the monocytic MDSC and polymorphonuclear MDSC phenotypes were both significantly increased in the blood of patients with GBM versus healthy controls. The myeloid activation markers CD80 and PD-L1 could not be detected on either of these MDSC subsets; CD124, CD86, and CD40 were detected at similar levels on MDSCs in patients with glioma and healthy donors. By contrast, in tumor cell suspensions, the MDSC population consisted almost exclusively of CD15-positive cells. Immunohistochemistry confirmed infiltration of CD15-positive major histocompatibility complex class II-negative cells in glioma tissue samples. These data support a role for cells with an MDSC phenotype in the blood and tumor microenvironment of patients with GBM.

Pieter Wesseling - One of the best experts on this subject based on the ideXlab platform.

  • increase in both CD14 positive and cd15 positive myeloid derived suppressor cell subpopulations in the blood of patients with glioma but predominance of cd15 positive myeloid derived suppressor cells in glioma tissue
    Journal of Neuropathology and Experimental Neurology, 2015
    Co-Authors: Paul R Gielen, Barbara M Schulte, Esther D Kersrebel, Kiek Verrijp, Harriette M J M Petersenbaltussen, Mark Ter Laan, Pieter Wesseling, Gosse J Adema
    Abstract:

    Myeloid-derived suppressor cells (MDSCs), defined as CD33-positive major histocompatibility complex class II-negative cells, are increased in a variety of human tumors and are associated with immunosuppression. Myeloid-derived suppressor cells can be further subdivided into CD14-positive monocytic MDSC and CD15-positive granulocytic MDSC (polymorphonuclear MDSC) subpopulations. Here we analyzed MDSC subsets in the blood and tumor tissue of patients with glioma, including the most malignant variant, glioblastoma multiforme (GBM). CD33-positive major histocompatibility complex class II-negative MDSCs in blood from 21 patients with glioma and 12 healthy individuals were phenotyped and quantified by flow cytometry. Myeloid populations of the monocytic MDSC and polymorphonuclear MDSC phenotypes were both significantly increased in the blood of patients with GBM versus healthy controls. The myeloid activation markers CD80 and PD-L1 could not be detected on either of these MDSC subsets; CD124, CD86, and CD40 were detected at similar levels on MDSCs in patients with glioma and healthy donors. By contrast, in tumor cell suspensions, the MDSC population consisted almost exclusively of CD15-positive cells. Immunohistochemistry confirmed infiltration of CD15-positive major histocompatibility complex class II-negative cells in glioma tissue samples. These data support a role for cells with an MDSC phenotype in the blood and tumor microenvironment of patients with GBM.

Gregory S Young - One of the best experts on this subject based on the ideXlab platform.

  • distinct myeloid suppressor cell subsets correlate with plasma il 6 and il 10 and reduced interferon alpha signaling in cd4 t cells from patients with gi malignancy
    Cancer Immunology Immunotherapy, 2011
    Co-Authors: Gregory S Young, Todd M Bauer, Elaine Binkley, Mark Bloomston, Bethany L Mundybosse
    Abstract:

    Interferon-alpha (IFN-α) promotes anti-tumor immunity through its actions on immune cells. We hypothesized that elevated percentages of myeloid-derived suppressor cells (MDSC) and increased pro-inflammatory cytokines in peripheral blood would be associated with impaired response to IFN-α in patients with gastrointestinal (GI) malignancies. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets, and IFN-α-induced signal transduction in 40 patients with GI malignancies. Plasma IL-6 and IL-10 were significantly higher in patients versus normal donors. CD33+HLADR−CD11b+CD15+ and CD33+HLADR−/lowCD14+ MDSC subsets were also elevated in patients versus normal donors (P < 0.0001). Plasma IL-6 was correlated with CD33+HLADR−CD15+ MDSC (P = 0.008) and IL-10 with CD33+HLADR−CD15− MDSC (P = 0.002). The percentage of CD15+ and CD15− but not CD14+ MDSC subsets were inversely correlated with IFN-α-induced STAT1 phosphorylation in CD4+ T cells, while co-culture with in vitro generated MDSC led to reduced IFN-α responsiveness in both PBMC and the CD4+ subset of T cells from normal donors. Exploratory multivariable Cox proportional hazards models revealed that an increased percentage of the CD33+HLADR−CD15− MDSC subset was associated with reduced overall survival (P = 0.049), while an increased percentage of the CD33+HLADR−/lowCD14+ subset was associated with greater overall survival (P = 0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets, and IFN-α responsiveness in patients with GI malignancies.

  • abstract 5517 distinct myeloid suppressor cell subsets correlate with plasma il 6 and il 10 and reduced interferon α signal transduction in cd4 t cells from patients with gastrointestinal malignancy
    Cancer Research, 2011
    Co-Authors: Bethany L Mundy, Gregory S Young, Todd M Bauer, Elaine Binkley, Mark Bloomston, Matthew A Bill, Tanios Bekaiisaab, William E Carson, Gregory B Lesinski
    Abstract:

    Interferon-alpha (IFNα) can promote anti-tumor immunity through its actions on immune cells. We have shown in murine models that a class of immune suppressor cells known as myeloid-derived suppressor cells (MDSC) have inhibitory effects on IFN signal transduction and gene regulation. Interleukin (IL)-6 and IL-10 are produced by tumor cells in cancer patients and can regulate the survival and function of MDSC. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets and IFNα-induced signal transduction in 40 patients with gastrointestinal (GI) malignancies. Plasma IL-6 and IL-10 levels were significantly higher in patients versus normal donors. CD33 + HLADR − CD11b + CD15 + and CD33 + HLADR −/low CD14 + MDSC were also elevated in patients versus normal donors (p + ) and monocytic (CD15 − ) subsets. Therefore relationships between CD15 expression on MDSC and cytokines elevated in GI patients were examined. A significant correlation between plasma IL-6 with CD33 + HLADRCD15 + MDSC (p=0.008) and IL10 with CD33 + HLADR − CD15 − MDSC (p=0.002) was observed. The level of CD15 + and CD15 − but not CD14 + MDSC subsets were inversely correlated with IFNα-induced STAT1 phosphorylation in CD4 + T cells, while co-culture with in vitro generated MDSC led to reduced IFNα-responsiveness in PBMC from normal donors. In a multivariable Cox proportional hazards model, an increased percentage of the CD33 + HLADR − CD15 − MDSC subset was associated with reduced overall survival (hazard ratio = 1.43; p = 0.049) while an increased percentage of the CD33 + HLADR −/low CD14 + subset was associated with greater overall survival (hazard ratio = 0.69, p=0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets and IFNα responsiveness in patients with GI malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5517. doi:10.1158/1538-7445.AM2011-5517

Elaine Binkley - One of the best experts on this subject based on the ideXlab platform.

  • distinct myeloid suppressor cell subsets correlate with plasma il 6 and il 10 and reduced interferon alpha signaling in cd4 t cells from patients with gi malignancy
    Cancer Immunology Immunotherapy, 2011
    Co-Authors: Gregory S Young, Todd M Bauer, Elaine Binkley, Mark Bloomston, Bethany L Mundybosse
    Abstract:

    Interferon-alpha (IFN-α) promotes anti-tumor immunity through its actions on immune cells. We hypothesized that elevated percentages of myeloid-derived suppressor cells (MDSC) and increased pro-inflammatory cytokines in peripheral blood would be associated with impaired response to IFN-α in patients with gastrointestinal (GI) malignancies. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets, and IFN-α-induced signal transduction in 40 patients with GI malignancies. Plasma IL-6 and IL-10 were significantly higher in patients versus normal donors. CD33+HLADR−CD11b+CD15+ and CD33+HLADR−/lowCD14+ MDSC subsets were also elevated in patients versus normal donors (P < 0.0001). Plasma IL-6 was correlated with CD33+HLADR−CD15+ MDSC (P = 0.008) and IL-10 with CD33+HLADR−CD15− MDSC (P = 0.002). The percentage of CD15+ and CD15− but not CD14+ MDSC subsets were inversely correlated with IFN-α-induced STAT1 phosphorylation in CD4+ T cells, while co-culture with in vitro generated MDSC led to reduced IFN-α responsiveness in both PBMC and the CD4+ subset of T cells from normal donors. Exploratory multivariable Cox proportional hazards models revealed that an increased percentage of the CD33+HLADR−CD15− MDSC subset was associated with reduced overall survival (P = 0.049), while an increased percentage of the CD33+HLADR−/lowCD14+ subset was associated with greater overall survival (P = 0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets, and IFN-α responsiveness in patients with GI malignancies.

  • abstract 5517 distinct myeloid suppressor cell subsets correlate with plasma il 6 and il 10 and reduced interferon α signal transduction in cd4 t cells from patients with gastrointestinal malignancy
    Cancer Research, 2011
    Co-Authors: Bethany L Mundy, Gregory S Young, Todd M Bauer, Elaine Binkley, Mark Bloomston, Matthew A Bill, Tanios Bekaiisaab, William E Carson, Gregory B Lesinski
    Abstract:

    Interferon-alpha (IFNα) can promote anti-tumor immunity through its actions on immune cells. We have shown in murine models that a class of immune suppressor cells known as myeloid-derived suppressor cells (MDSC) have inhibitory effects on IFN signal transduction and gene regulation. Interleukin (IL)-6 and IL-10 are produced by tumor cells in cancer patients and can regulate the survival and function of MDSC. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets and IFNα-induced signal transduction in 40 patients with gastrointestinal (GI) malignancies. Plasma IL-6 and IL-10 levels were significantly higher in patients versus normal donors. CD33 + HLADR − CD11b + CD15 + and CD33 + HLADR −/low CD14 + MDSC were also elevated in patients versus normal donors (p + ) and monocytic (CD15 − ) subsets. Therefore relationships between CD15 expression on MDSC and cytokines elevated in GI patients were examined. A significant correlation between plasma IL-6 with CD33 + HLADRCD15 + MDSC (p=0.008) and IL10 with CD33 + HLADR − CD15 − MDSC (p=0.002) was observed. The level of CD15 + and CD15 − but not CD14 + MDSC subsets were inversely correlated with IFNα-induced STAT1 phosphorylation in CD4 + T cells, while co-culture with in vitro generated MDSC led to reduced IFNα-responsiveness in PBMC from normal donors. In a multivariable Cox proportional hazards model, an increased percentage of the CD33 + HLADR − CD15 − MDSC subset was associated with reduced overall survival (hazard ratio = 1.43; p = 0.049) while an increased percentage of the CD33 + HLADR −/low CD14 + subset was associated with greater overall survival (hazard ratio = 0.69, p=0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets and IFNα responsiveness in patients with GI malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5517. doi:10.1158/1538-7445.AM2011-5517