Hematopoietic stem cell involvement in positive ALL as a potential mechanism of resistance to blinatumomab therapy.

The bispecific T-cell engager blinatumomab targeting CD19 can induce complete remission in relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, some patients ultimately relapse with loss of CD19 antigen on leukemic cells, which has been established as a novel mechanism to escape CD19-specific immunotherapies. Here, we provide evidence that CD19-negative (CD19) relapse after CD19-directed therapy in BCP-ALL may be a result of the selection of preexisting CD19 malignant progenitor cells.

[Successful closure of a postoperative esophagobronchial fistula following esophageal resection using fibrin glue].

Unlabelled: HISTORY AND INTERVENTION: A 52-year-old female patient underwent open abdominothoracic cardia and esophageal resection with gastric transposition because of histologically diagnosed Barrett metaplasia with "high-grade" intraepithelial neoplasia (HGIEN) and parts of an invasive adenocarcinoma. The anastomotic insufficiency on the 10th postoperative day including an esophagobronchial fistula prompted to a subsequent surgical re-intervention with suture of the fistula, lavage and additional drainage, an endoscopic stenting of the fistula from esophageal site, as well as repeated (n = 22) bronchoscopic applications of fibrin glue (1-3 ml each) into the lumen of the fistula after each bronchoscopic lavage of the fistula until the complete closure was achieved. The changeful clinical course of 77 days on the surgical ICU was characterized by secondary complications such as pneumonia, mediastinitis and respiratory insufficiency with long-term artificial respiration and creation of a percutaneous dilatation tracheotomy.

Human NK cells require caspases for activation-induced proliferation and cytokine release but not for cytotoxicity.

Natural killer (NK) cells are innate immune cells involved in antiviral defence and tumour surveillance. To fulfil these tasks, NK cells make use of two major effector functions, cytokine and chemokine release and cytotoxicity. In addition, NK cells proliferate in response to cytokines such as IL-2.

Differential but direct abolishment of human regulatory T cell suppressive capacity by various TLR2 ligands.

CD4(+)CD25(high) regulatory T cells (Tregs) control cellular immune responses and maintain peripheral tolerance. We investigated whether TLR2 ligands are able to abrogate Treg-induced suppression in humans based on different reports about effects of triacylated lipopeptide Pam(3)CSK4 in mice. Pretreatment of human Tregs with a mixture of TLR2 ligands Pam(2)CSK4, FSL-1, and Pam(3)CSK4 reduced the Treg-mediated suppression of CD4(+)CD25(-) responder T cells in the majority of the analyzed donors.

Interaction with XIAP prevents full caspase-3/-7 activation in proliferating human T lymphocytes.

Caspases are essential mediators of cytokine release and apoptosis. Additionally, caspase activity is required for the proliferation of naive T lymphocytes. It remained unclear how proliferating cells are able to cope with the pro-apoptotic activity especially of effector caspases-3 and -7.