Browsing by Subject "Tumour microenvironment"

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    Immunosuppressive cells and tumour microenvironment: Focus on mesenchymal stem cells and myeloid derived suppressor cells
    (F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Bianchi, Giovanna; Borgonovo, Giacomo; Pistoia, Vito; Raffaghello, Lizzia
    Tumours have been compared to unhealed wounds that produce large amounts of inflammatory mediators, including cytokines, chemokines, and growth factors. These molecules participate in the formation of a rich and heterogeneous microenvironment by attracting non malignant cells that promote tumour progression and dissemination. Tumour infiltrating cells include macrophages, myeloid-derived suppressor cells (MDSCs), mesenchymal stromal cells (MSCs) and TIE2-expressing monocytes. Most of them are bone marrow-derived, although MSC are present in virtually every tissue. This review focuses on MDSCs and MSCs, both of which can exert pro-tumorigenic effects through negative regulation of immune responses. MDSCs represent a heterogeneous population of cells of myeloid origin that are expanded and activated in response to growth factors and cytokines released by tumours. Once MDSCs are activated, they accumulate in lymphoid organs and tumours where they exert T cell immunosuppression. Like MDSCs, MSCs can be mobilized from the bone marrow into the bloodstream and home in the tumour stroma, where they either help or hinder tumour growth. Here, we will discuss the origin, the functions and the mechanisms of action of MSCs and MDSCs, as well as the strategies to target these cells for the therapeutic benefit of cancer patients.
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    The relationship between members of the canonical NF-kB pathway, tumour microenvironment and cancer specific survival in colorectal cancer patients
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Quinn, Jean A; Bennett, Lindsay; Patel, Meera; Frixou, Mikaela; Park, James H.; Roseweir, Antonia; Horgan, Paul G; McMillan, Donald C; Edwards, Joanne
    Background. The aim of this study was to investigate the role of the upstream kinase TAK1 and the canonical NF-κB pathway in colorectal cancer (CRC). Immunohistochemistry was used to assess the expression of TAK1/pTAK1 and canonical NF-κB pathway members in a tissue microarray of 242 patients. The relationship between expression, the tumour microenvironment and cancer-specific survival were examined. Results. All the investigated members of the pathway were expressed in CRC tissue. In addition, cytoplasmic pTAK1 was associated with the tumour microenvironment (P=0.045) and cancer- specific survival (CSS) (P=0.032). When cytoplasmic pTAK1 was stratified by BRAF status, cytoplasmic pTAK1 expression association with CSS was strengthened (P=0.014). Cytoplasmic IKKβ was significantly associated with the inflammatory cell infiltrate (P=0.015) as graded by Klintrup Makinen grade, systemic inflammation as assessed by neutrophil- lymphocyte ratio (P=0.03) and CSS (P=0.046). On multivariate analysis cytoplasmic IKKβ was independently associated with CSS (HR 1.75,95%CI 1.05-2.91, P=0.033). Conclusion. Cytoplasmic pTAK1 was significantly associated with CSS and this was enhanced in patients with tumours that expressed wild type BRAF. High expression of cytoplasmic IKKβ was significantly associated with decreased CSS and with markers of the tumour microenvironment. These results support the hypothesis that NF-κB pathway members are poor prognostic markers in patients with CRC, but this requires to be validated in a large independent cohort