Inflammation plays crucial roles at different stages of tumor development and may lead to the failure of immune surveillance and immunotherapy. Tumor-associated inflammatory microenvironment contains both innate and adaptive immune cells that communicate each other and engage a dynamic crosstalk with cancer cells (Grivennikov et al., 2010). Myeloid-derived suppressor cells (MDSC) are one of the major components of the immune-suppressive network that favors tumor growth (Gabrilovich and Nagaraj, 2009). Due to their tissue distribution and their capability to release a large spectrum of mediators after stimulation, mast cells (MC) act as potential regulatory linkers between innate and acquired immunity in the control of immune system homeostasis (Frossi et al., 2004), but they are also implicated in the promotion of tumor growth (Maltby et al., 2009). The aim of this work was to characterize the role of MCs in a colon cancer model and to investigate the possibility of MC interaction with MDSCs in the control of tumor-induced immune response. Obtained results demonstrated that MCs were recruited and had potential pro- tumoral functions in the growth of CT-26 colon cancer. At the same time, the tumor induced the accumulation of CD11b+ Gr-1+ immature MDSCs, which caused profound alteration of antitumor immune response. In the spleen, conditioned by the inflammatory response to tumor growth, MCs seemed to be able to directly contact accumulating MDSCs and direct their activation triggered by tumor specific IFN-γ-producing CD4+ T cells. In fact, ex vivo MCs emerged for their ability to switch on the suppressive properties of spleen-derived monocytic-MDSCs, rendering them able to inhibit polyclonal antigen-non-specific activation through increased production of nitric oxide. In addiction, the CD40:CD40L cross talk between the two populations was responsible for the instauration of a pro-inflammatory microenvironment, with the exacerbation in the production of mediators that can further support MDSC mobilization and tumor growth

Interacting mast cells and myeloid derived suppressor cells in the regulation of tumor-specific immune response / Luca Danelli - Udine : . , 2013 Apr 12. ((25. ciclo

Interacting mast cells and myeloid derived suppressor cells in the regulation of tumor-specific immune response

Danelli, Luca
2013-04-12

Abstract

Inflammation plays crucial roles at different stages of tumor development and may lead to the failure of immune surveillance and immunotherapy. Tumor-associated inflammatory microenvironment contains both innate and adaptive immune cells that communicate each other and engage a dynamic crosstalk with cancer cells (Grivennikov et al., 2010). Myeloid-derived suppressor cells (MDSC) are one of the major components of the immune-suppressive network that favors tumor growth (Gabrilovich and Nagaraj, 2009). Due to their tissue distribution and their capability to release a large spectrum of mediators after stimulation, mast cells (MC) act as potential regulatory linkers between innate and acquired immunity in the control of immune system homeostasis (Frossi et al., 2004), but they are also implicated in the promotion of tumor growth (Maltby et al., 2009). The aim of this work was to characterize the role of MCs in a colon cancer model and to investigate the possibility of MC interaction with MDSCs in the control of tumor-induced immune response. Obtained results demonstrated that MCs were recruited and had potential pro- tumoral functions in the growth of CT-26 colon cancer. At the same time, the tumor induced the accumulation of CD11b+ Gr-1+ immature MDSCs, which caused profound alteration of antitumor immune response. In the spleen, conditioned by the inflammatory response to tumor growth, MCs seemed to be able to directly contact accumulating MDSCs and direct their activation triggered by tumor specific IFN-γ-producing CD4+ T cells. In fact, ex vivo MCs emerged for their ability to switch on the suppressive properties of spleen-derived monocytic-MDSCs, rendering them able to inhibit polyclonal antigen-non-specific activation through increased production of nitric oxide. In addiction, the CD40:CD40L cross talk between the two populations was responsible for the instauration of a pro-inflammatory microenvironment, with the exacerbation in the production of mediators that can further support MDSC mobilization and tumor growth
Tumor microenvironment; Colon cancer; Mast cells; Myeloid derived suppressor cells; Immune suppression
Interacting mast cells and myeloid derived suppressor cells in the regulation of tumor-specific immune response / Luca Danelli - Udine : . , 2013 Apr 12. ((25. ciclo
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11390/1132626
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