CD16+ as predictive marker for early relapse in aggressive B-NHL/DLBCL patients.

Assessing the prognosis of patients with aggressive non-Hodgkin B cell lymphoma mainly relies on a clinical risk score (IPI). Standard first-line therapies are based on a chemo-immunotherapy with rituximab, which mediates CD16-dependent antibody-dependent cellular cytotoxicity (ADCC). We phenotypically and functionally analyzed blood samples from 46 patients focusing on CD16+ NK cells, CD16+ T cells and CD16+ monocytes.

Identification of molecular candidates which regulate calcium-dependent CD8 T-cell cytotoxicity.

Cytotoxic CD8 T lymphocytes (CTL) eliminate infected cells or transformed tumor cells by releasing perforin-containing cytotoxic granules at the immunological synapse. The secretion of such granules depends on Ca-influx through store operated Ca channels, formed by STIM (stromal interaction molecule)-activated Orai proteins. Whereas molecular mechanisms of the secretion machinery are well understood, much less is known about the molecular machinery that regulates the efficiency of Ca-dependent target cell killing.

Interdependence of sequential cytotoxic T lymphocyte and natural killer cell cytotoxicity against melanoma cells.

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells recognize and eliminate cancer cells. However, immune evasion, downregulation of immune function by the tumour microenvironment and resistance of cancer cells are major problems. Although CTL and NK cells are both important to eliminate cancer, most studies address them individually.

A calcium optimum for cytotoxic T lymphocyte and natural killer cell cytotoxicity.

Key Points: Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are required to eliminate cancer cells. We analysed the Ca dependence of CTL and NK cell cytotoxicity and found that in particular CTLs have a very low optimum of [Ca ] (between 122 and 334 nm) and [Ca ] (between 23 and 625 μm) for efficient cancer cell elimination, well below blood plasma Ca levels. As predicted from these results, partial down-regulation of the Ca channel Orai1 in CTLs paradoxically increases perforin-dependent cancer cell killing.

Syntaxin 8 is required for efficient lytic granule trafficking in cytotoxic T lymphocytes.

Cytotoxic T lymphocytes (CTL) eliminate pathogen-infected and cancerous cells mainly by polarized secretion of lytic granules (LG, containing cytotoxic molecules like perforin and granzymes) at the immunological synapse (IS). Members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family are involved in trafficking (generation, transport and fusion) of vesicles at the IS. Syntaxin 8 (Stx8) is expressed in LG and colocalizes with the T cell receptor (TCR) upon IS formation.

Deep characterization of blood cell miRNomes by NGS.

A systematic understanding of different factors influencing cell type specific microRNA profiles is essential for state-of-the art biomarker research. We carried out a comprehensive analysis of the biological variability and changes in cell type pattern over time for different cell types and different isolation approaches in technical replicates. All combinations of the parameters mentioned above have been measured, resulting in 108 miRNA profiles that were evaluated by next-generation-sequencing.