Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity

<p>Abstract</p> <p>Background</p> <p>Tumour growth and metastatic infiltration are favoured by several components of the tumour microenvironment. Bone marrow-derived multipotent mesenchymal stromal cells (MSC) are known to contribute to the tumour stroma. When isolated from healthy bone marrow, MSC exert potent antiproliferative effects on immune effector cells. Due to phenotypic and morphological similarities of MSC and tumour stromal cells (TStrC), we speculated that immunotherapeutic approaches may be hampered if TStrC may still exhibit immunomodulatory properties of MSC.</p> <p>Methods</p> <p>In order to compare immunomodulatory properties of MSC and tumour stromal cells (TStrC), we established and analyzed TStrC cultures from eleven paediatric tumours and MSC preparations from bone marrow aspirates. Immunophenotyping, proliferation assays and NK cell cytotoxicity assays were employed to address the issue.</p> <p>Results</p> <p>While TStrC differed from MSC in terms of plasticity, they shared surface expression of CD105, CD73 and other markers used for MSC characterization. Furthermore, TStrC displayed a strong antiproliferative effect on peripheral blood mononuclear cells (PBMC) in coculture experiments similar to MSC. NK cell cytotoxicity was significantly impaired after co-culture with TStrC and expression of the activating NK cell receptors NKp44 and NKp46 was reduced.</p> <p>Conclusions</p> <p>Our data show that TStrC and MSC share important phenotypic and functional characteristics. The inhibitory effect of TStrC on PBMC and especially on NK cells may facilitate the immune evasion of paediatric tumours.</p

Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients

Activity of cetuximab, a chimeric monoclonal antibody targeting the epidermal growth factor receptor, is largely attributed to its direct antiproliferative and proapoptotic effects. Antibody-dependent cell-mediated cytotoxicity (ADCC) could be another possible mechanism of cetuximab antitumor effects and its specific contribution on the clinical activity of cetuximab is unknown.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Implementation of long solids retention time activated sludge process for rural residential community

Most rural communities in the United States are facing increasingly rigorous effluent criteria, especially ammonia, for their wastewater treatment facilities. A new baffled bioreactor (BBR) technology, which employs a preanoxic activated sludge process operated with a long solids retention time (SRT), was installed in a small community in Missouri to address the more stringent effluent limits. In a recent full-year normal operation cycle (2018), the average effluent concentrations of BOD5, TSS, and ammonia-nitrogen were 3.2, 2.2, and 0.5 mg/L, respectively, with removal efficiencies of 96%, 85%, and 98%, respectively. All these parameters were significantly better than their respective permit limits. The long SRT afforded an enhanced factor of safety for the process, conferring the ability to nitrify at sustained ambient temperatures as low as −22°C. Long SRT also resulted in significant reductions in waste sludge production, resulting in dramatically reduced operational costs for sludge handling. Ultimately, the long SRT activated sludge process afforded the ability to meet stringent effluent quality standards including ammonia and the numerous unique challenges that are inherent to small flows. Practitioner points: Small community hydraulic and mass loadings are highly variable and difficult to quantify during facility design. A long SRT activated sludge process warrants superior performance and enhanced factor of safety. The long SRT process with preanoxic zones generated no excess sludge during the extended operation period, significantly simplifying plant operation. Long SRT process is well suited to accommodate wastewater variability associated with small communities while maintaining superior treatment quality