Tumor Cell Biology

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Jose L Quiles - One of the best experts on this subject based on the ideXlab platform.

Maurizio Battino - One of the best experts on this subject based on the ideXlab platform.

Francesca Giampieri - One of the best experts on this subject based on the ideXlab platform.

Christoph Domschke - One of the best experts on this subject based on the ideXlab platform.

  • determination of paraneoplastic autoimmune responses by Tumor Cell Biology and intraTumoral ifn alpha il 12 in breast cancer patients
    Cancer Immunology Immunotherapy, 2011
    Co-Authors: Christoph Domschke, Florian Schuetz, Yingzi Ge, Hanspeter Sinn, Markus Zorn, Frederik Marme, Sarah Schott, Joerg Heil, A Scharf, Christof Sohn
    Abstract:

    A wide variety of cancer types has been associated with paraneoplastic autoimmune disorders and with the induction of autoimmunity against several autoantigens, among them self-antigens that are also expressed by Tumor Cells. This raises the question of autoimmune disorders as a result of immune reactions to the Tumor. To date, however, requirements for the generation of autoimmune reactions in cancer patients remain largely unclear. In this study, we characterized conditions in altogether 131 patients, which determine autoimmune responses in primary breast cancer patients. We used ex vivo IFN-γ EliSpot assays against autologous Tumor or skin lysates to evaluate Tumor- and auto-reactive T-Cells (TCs) in the bone marrow (BM) as well as ELISA, ECLIA, and turbidimetric immunoassays for the detection of auto-reactive antibodies in the peripheral blood and compared results to intraTumoral cytokine concentrations and pathobiological features of the primary Tumor tissue. We here demonstrate a significant correlation between anti-Tumor BMTC responses and Cellular autoimmune reactivity in primary breast cancer patients (P = 0.002). Humoral autoimmune reactions, however, were negatively correlated with anti-Tumor TC immunity (P = 0.039). We observed auto-reactive BMTCs especially in patients with well-differentiated, hormone receptor-positive carcinomas (P = 0.009). Furthermore, elevated concentrations of intraTumoral IFN-α significantly correlated with the induction of Cellular autoimmune reactivity (P = 0.0002), while humoral autoimmune reactions correlated with increased levels of intraTumoral IL-12 (P = 0.04). Altogether, these data indicate a significant role of the Tumor microenvironment and particularly that of IFN-α and IL-12 in the induction of systemic autoimmune responses and imply that the primary Tumor tissue represents an integral site of autoimmune regulation in cancer patients.

  • Determination of paraneoplastic autoimmune responses by Tumor Cell Biology and intraTumoral IFN-alpha/IL-12 in breast cancer patients
    Cancer Immunology Immunotherapy, 2010
    Co-Authors: Christoph Domschke, Florian Schuetz, Yingzi Ge, Hanspeter Sinn, Markus Zorn, Frederik Marme, Sarah Schott, Joerg Heil, A Scharf
    Abstract:

    A wide variety of cancer types has been associated with paraneoplastic autoimmune disorders and with the induction of autoimmunity against several autoantigens, among them self-antigens that are also expressed by Tumor Cells. This raises the question of autoimmune disorders as a result of immune reactions to the Tumor. To date, however, requirements for the generation of autoimmune reactions in cancer patients remain largely unclear. In this study, we characterized conditions in altogether 131 patients, which determine autoimmune responses in primary breast cancer patients. We used ex vivo IFN-γ EliSpot assays against autologous Tumor or skin lysates to evaluate Tumor- and auto-reactive T-Cells (TCs) in the bone marrow (BM) as well as ELISA, ECLIA, and turbidimetric immunoassays for the detection of auto-reactive antibodies in the peripheral blood and compared results to intraTumoral cytokine concentrations and pathobiological features of the primary Tumor tissue. We here demonstrate a significant correlation between anti-Tumor BMTC responses and Cellular autoimmune reactivity in primary breast cancer patients (P = 0.002). Humoral autoimmune reactions, however, were negatively correlated with anti-Tumor TC immunity (P = 0.039). We observed auto-reactive BMTCs especially in patients with well-differentiated, hormone receptor-positive carcinomas (P = 0.009). Furthermore, elevated concentrations of intraTumoral IFN-α significantly correlated with the induction of Cellular autoimmune reactivity (P = 0.0002), while humoral autoimmune reactions correlated with increased levels of intraTumoral IL-12 (P = 0.04). Altogether, these data indicate a significant role of the Tumor microenvironment and particularly that of IFN-α and IL-12 in the induction of systemic autoimmune responses and imply that the primary Tumor tissue represents an integral site of autoimmune regulation in cancer patients.

  • intraTumoral cytokines and Tumor Cell Biology determine spontaneous breast cancer specific immune responses and their correlation to prognosis
    Cancer Research, 2009
    Co-Authors: Christoph Domschke, Florian Schuetz, Yingzi Ge, Tobias Seibel, Christine S Falk, Benedikt Brors, Israel Vlodavsky, Nora Sommerfeldt, Hanspeter Sinn, Mariechristine Kuhnle
    Abstract:

    Spontaneous immune responses in cancer patients have been described. Yet their clinical relevance and the conditions for their generation remain unclear. We characterized conditions that determine immune responses in primary breast cancer patients. We used tetramer analysis, ex vivo IFN-γ ELISPOT, cytotoxicity assays, and ELISA in 207 untreated patients and 12 Her-2/neu–specific CD8 T-Cell lines to evaluate Tumor-specific T Cells (TC) in the bone marrow or MUC1-specific antibodies in the blood. Multiplex analysis was performed to quantify 27 intraTumoral cytokines, chemokines, and growth factors. Results were compared with multiple pathologic and clinical parameters of the patients and Tumors. Forty percent of the patients showed Tumor-specific TC responses. These correlated with Tumors of high differentiation, estrogen receptor expression, and low proliferative activity, and with a reduced cancer mortality risk. High Tumor Cell differentiation correlated with increased intraTumoral, but not plasma, concentrations of IFN-α and reduced transforming growth factor (TGF)β1. In an in vitro priming experiment these two cytokines increased or inhibited, respectively, the capacity of dendritic Cells to induce Tumor-reactive TC. Tumor-specific B-Cell responses, mainly of IgM isotype, were detectable in 50% of the patients and correlated with advanced Tumor stage, increased TGFβ1, reduced IFN-α, and absence of TC responses. We show here that different types of immune responses are linked to distinct cytokine microenvironments and correlate with prognosis-relevant differences in Tumor pathoBiology. These findings shed light on the relation between immune response and cancer prognosis. [Cancer Res 2009;69(21):8420–8]

  • IntraTumoral Cytokines and Tumor Cell Biology Determine Spontaneous Breast Cancer–Specific Immune Responses and Their Correlation to Prognosis
    Cancer Research, 2009
    Co-Authors: Christoph Domschke, Florian Schuetz, Yingzi Ge, Tobias Seibel, Christine S Falk, Benedikt Brors, Israel Vlodavsky, Nora Sommerfeldt, Hanspeter Sinn, Mariechristine Kuhnle
    Abstract:

    Spontaneous immune responses in cancer patients have been described. Yet their clinical relevance and the conditions for their generation remain unclear. We characterized conditions that determine immune responses in primary breast cancer patients. We used tetramer analysis, ex vivo IFN-γ ELISPOT, cytotoxicity assays, and ELISA in 207 untreated patients and 12 Her-2/neu–specific CD8 T-Cell lines to evaluate Tumor-specific T Cells (TC) in the bone marrow or MUC1-specific antibodies in the blood. Multiplex analysis was performed to quantify 27 intraTumoral cytokines, chemokines, and growth factors. Results were compared with multiple pathologic and clinical parameters of the patients and Tumors. Forty percent of the patients showed Tumor-specific TC responses. These correlated with Tumors of high differentiation, estrogen receptor expression, and low proliferative activity, and with a reduced cancer mortality risk. High Tumor Cell differentiation correlated with increased intraTumoral, but not plasma, concentrations of IFN-α and reduced transforming growth factor (TGF)β1. In an in vitro priming experiment these two cytokines increased or inhibited, respectively, the capacity of dendritic Cells to induce Tumor-reactive TC. Tumor-specific B-Cell responses, mainly of IgM isotype, were detectable in 50% of the patients and correlated with advanced Tumor stage, increased TGFβ1, reduced IFN-α, and absence of TC responses. We show here that different types of immune responses are linked to distinct cytokine microenvironments and correlate with prognosis-relevant differences in Tumor pathoBiology. These findings shed light on the relation between immune response and cancer prognosis. [Cancer Res 2009;69(21):8420–8]

Eric Chevet - One of the best experts on this subject based on the ideXlab platform.

  • p97 cdc 48 proteostasis control in Tumor Cell Biology
    Cancer Letters, 2013
    Co-Authors: Delphine Fessart, Esther Marza, Said Taouji, Frederic Delom, Eric Chevet
    Abstract:

    P97/CDC-48 is a prominent member of a highly evolutionary conserved Walker cassette – containing AAA + ATPases. It has been involved in numerous Cellular processes ranging from the control of protein homeostasis to membrane trafficking through the intervention of specific accessory proteins. Expression of p97/CDC-48 in cancers has been correlated with Tumor aggressiveness and prognosis, however the precise underlying molecular mechanisms remain to be characterized. Moreover p97/CDC-48 inhibitors were developed and are currently under intense investigation as anticancer drugs. Herein, we discuss the role of p97/CDC-48 in cancer development and its therapeutic potential in Tumor Cell Biology.

  • P97/CDC-48: Proteostasis control in Tumor Cell Biology
    Cancer Letters, 2013
    Co-Authors: Delphine Fessart, Esther Marza, Said Taouji, Frederic Delom, Eric Chevet
    Abstract:

    P97/CDC-48 is a prominent member of a highly evolutionary conserved Walker cassette – containing AAA + ATPases. It has been involved in numerous Cellular processes ranging from the control of protein homeostasis to membrane trafficking through the intervention of specific accessory proteins. Expression of p97/CDC-48 in cancers has been correlated with Tumor aggressiveness and prognosis, however the precise underlying molecular mechanisms remain to be characterized. Moreover p97/CDC-48 inhibitors were developed and are currently under intense investigation as anticancer drugs. Herein, we discuss the role of p97/CDC-48 in cancer development and its therapeutic potential in Tumor Cell Biology.