TIGIT expressing CD4+T cells represent a tumor-supportive T cell subset in chronic lymphocytic leukemia

While research on T cell exhaustion in context of cancer particularly focuses on CD8C cytotoxic T cells, the role of inhibitory receptors on CD4C T-helper cells have remained largely unexplored. TIGIT is a recently identified inhibitory receptor on T cells and natural killer (NK) cells. In this study, we examined TIGIT expression on T cell subsets from CLL patients. While we did not observe any differences in TIGIT expression in CD8C T cells of healthy controls and CLL cells, we found an enrichment of TIGITC T cells in the CD4C T cell compartment in CLL. Intriguingly, CLL patients with an advanced disease stage displayed elevated numbers of CD4C TIGITC T cells compared to low risk patients. Autologous CLL-T cell co-culture assays revealed that depleting CD4C TIGITC expressing T cells from co-cultures significantly decreased CLL viability. Accordingly, a supportive effect of TIGITCCD4C T cells on CLL cells in vitro could be recapitulated by blocking the interaction of TIGIT with its ligands using TIGIT-Fc molecules, which also impeded the T cell specific production of CLL-prosurvival cytokines. Our data reveal that TIGITCCD4CT cells provide a supportive microenvironment for CLL cells, representing a potential therapeutic target for CLL treatment

Management of Solid-pseudopapillary Neoplasms of the Pancreas: a Comparison with Standard Pancreatic Neoplasms

BACKGROUND: Solid-pseudopapillary neoplasms (SPNs) of the pancreas are increasingly diagnosed, but the exact surgical management in terms of extent of the resection is not well defined. MATERIALS AND METHODS: Patients operated on in our hospital between January 1993 and March 2005 formed the study groups. RESULTS: From 659 consecutive resections for pancreatic neoplasms, 12 female patients (1.8%) with a median age of 21 years who underwent resection for (SPN) are compared with the remaining 647 pancreatic resection patients. Jaundice (SPN 0 versus PR 73%, p < 0.001) and weight loss (SPN 0 versus PR 49%, p = 0.001) occurred significantly less often. Neoplasms were distributed equally among the pancreatic head (SPN 5 out of 12 patients versus PR 88%, p < 0.001) and corpus/tail (SPN 6 out of 12 patients versus PR 8%, p < 0.001). The operative time was significantly shorter (SPN 233 min versus PR 280 min, p = 0.012), and there were significantly fewer complications (SPN 1 of 12 patients versus PR 48%, p = 0.007). The mortality was not different (SPN 0 versus PR 1.6%, p = 1.000), and the hospital stay was significantly shorter (SPN 9 days versus PR 15 days, p = 0.012). The median size of the neoplasms was significantly larger (SPN 6.9 cm versus PR 2.5 cm). The median number of lymph nodes harvested was significantly fewer (SPN 1 versus PR 6, p = 0.001), and lymph node metastases occurred significantly less often (SPN 0 versus PR 64%, p < 0.001). The 5-year survival of SPN patients was 100% and is significantly better compared with survival of patients with pancreatic adenocarcinoma (12%, p < 0.001) and ampulla of Vater adenocarcinoma (22%, p = 0.005). CONCLUSIONS: Patients with solid-pseudopapillary neoplasms of the pancreas present differently and the course of the disease is more benign. These patients can be adequately managed by pylorus-preserving pancreatoduodenectomy or spleen-preserving distal pancreatectomy with excellent early and long-term result

Release of Toxic Metals from Button Batteries Retained in the Stomach : An in Vitro Study.

Background. Ingestion of button batteries by children is a rapidly growing problem, and opinions differ on how button batteries distal to the gastroesophageal junction should be managed. The authors therefore performed an experimental study to determine the cumulative load of various toxic elements released from retained button cells in simulated gastric juice.Methods: Eight different groups of button cells were immersed in simulated gastric juice. Analyzed elements included Al, Ba, Cd, Cr, Cu, Fe, Hg, Li, Mg, Mn, Ni, Pb, Sb, Sn, Sr, Te, Tl, V, W; and Zn. Inductively coupled plasma mass spectrometry (ICP-MS) was used to evaluate the residual amounts of elements after 4, 24, 72, and 120 hours.Results: At 4 hours, leakage was seen with almost all batteries, with the levels increasing in a time-dependent manner. The highest detected levels at 4 hours were 1.20 mug for Cd, 280.51 ng for Hg, and 2.63 mug for Pb. Dissolution, holes, and defragmentation were seen within 24 to 72 hours. Battery weight loss varied between 22 and 104 mg over the course of the study.Conclusions: Toxic elements contained in button cells are released quickly in gastric juice. This finding might change the current policy of watchful waiting or conservative management of batteries lodged in the stomach