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  1. Article ; Online: Macrophage-Mediated Melanoma Reduction after HP-NAP Treatment in a Zebrafish Xenograft Model

    Gaia Codolo / Nicola Facchinello / Nicole Papa / Ambra Bertocco / Sara Coletta / Clara Benna / Luigi Dall’Olmo / Simone Mocellin / Natascia Tiso / Marina de Bernard

    International Journal of Molecular Sciences, Vol 23, Iss 1644, p

    2022  Volume 1644

    Abstract: The Helicobacter pylori Neutrophil Activating Protein (HP-NAP) is endowed with immunomodulatory properties that make it a potential candidate for anticancer therapeutic applications. By activating cytotoxic Th1 responses, HP-NAP inhibits the growth of ... ...

    Abstract The Helicobacter pylori Neutrophil Activating Protein (HP-NAP) is endowed with immunomodulatory properties that make it a potential candidate for anticancer therapeutic applications. By activating cytotoxic Th1 responses, HP-NAP inhibits the growth of bladder cancer and enhances the anti-tumor activity of oncolytic viruses in the treatment of metastatic breast cancer and neuroendocrine tumors. The possibility that HP-NAP exerts its anti-tumor effect also by modulating the activity of innate immune cells has not yet been explored. Taking advantage of the zebrafish model, we examined the therapeutic efficacy of HP-NAP against metastatic human melanoma, limiting the observational window to 9 days post-fertilization, well before the maturation of the adaptive immunity. Human melanoma cells were xenotransplanted into zebrafish embryos and tracked in the presence or absence of HP-NAP. The behavior and phenotype of macrophages and the impact of their drug-induced depletion were analyzed exploiting macrophage-expressed transgenes. HP-NAP administration efficiently inhibited tumor growth and metastasis and this was accompanied by strong recruitment of macrophages with a pro-inflammatory profile at the tumor site. The depletion of macrophages almost completely abrogated the ability of HP-NAP to counteract tumor growth. Our findings highlight the pivotal role of activated macrophages in counteracting melanoma growth and support the notion that HP-NAP might become a new biological therapeutic agent for the treatment of metastatic melanomas.
    Keywords HP-NAP ; melanoma ; zebrafish ; macrophages ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The immune receptor CD300e negatively regulates T cell activation by impairing the STAT1-dependent antigen presentation

    Sara Coletta / Valentina Salvi / Chiara Della Bella / Ambra Bertocco / Silvia Lonardi / Elisabetta Trevellin / Matteo Fassan / Mario M. D’Elios / William Vermi / Roberto Vettor / Stefano Cagnin / Silvano Sozzani / Gaia Codolo / Marina de Bernard

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 13

    Abstract: Abstract CD300e is a surface receptor, expressed by myeloid cells, involved in the tuning of immune responses. CD300e engagement was reported to provide the cells with survival signals, to trigger the expression of activation markers and the release of ... ...

    Abstract Abstract CD300e is a surface receptor, expressed by myeloid cells, involved in the tuning of immune responses. CD300e engagement was reported to provide the cells with survival signals, to trigger the expression of activation markers and the release of pro-inflammatory cytokines. Hence, CD300e is considered an immune activating receptor. In this study, we demonstrate that the ligation of CD300e in monocytes hampers the expression of the human leukocyte antigen (HLA) class II, affecting its synthesis. This effect, which is associated with the transcription impairment of the signal transducer and activator of transcription 1 (STAT1), overcomes the capacity of interferon gamma (IFN-γ) to promote the expression of the antigen-presenting molecules. Importantly, the decreased expression of HLA-II on the surface of CD300e-activated monocytes negatively impacts their capacity to activate T cells in an antigen-specific manner. Notably, unlike in vitro- differentiated macrophages which do not express CD300e, the immune receptor is expressed by tissue macrophages. Taken together, our findings argue against the possibility that this molecule should be considered an activating immune receptor sensu stricto. Moreover, our results support the notion that CD300e might be a new player in the regulation of the expansion of T cell-mediated responses.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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