BackgroundTumor response to immunotherapy is the consequence of a concerted crosstalk between cytokines and effector cells. Interferon gamma (IFNγ) is one of the common cytokines coordinating tumor immune response and the associated biological consequences. Although the role of IFNγ in the modulation of tumor immunity has been widely documented, the mechanisms regulating IFNγ-induced cell death, during the course of immune therapy, is not described in detail.ResultsIFNγ triggered apoptosis of CLS-354 and RPMI 2650 cells, enhanced the protein expression and activation of indoleamine 2,3-dioxygenase (IDO), and suppressed the basal expression of heme oxygenase-1(HO-1). Interestingly, IFNγ induced the loss of mitochondrial membrane potential (Δψm) and increased accumulation of reactive oxygen species (ROS). The cytokine also induced the activation of Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT)1, apoptosis signal-regulating kinase 1 (ASK1), p38, c-jun-N-terminal kinase (JNK) and NF-κB pathways and the transcription factors STAT1, interferon regulatory factor 1 (IRF1), AP-1, ATF-2, NF-κB and p53, and expression of Noxa protein. Furthermore, IFNγ was found to trigger endoplasmic reticulum (ER) stress as evidenced by the cleavage of caspase-4 and activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol-requiring-1α (IRE1α) pathways. Using specific inhibitors, we identified a potential role for IDO as apoptotic mediator in the regulation of IFNγ-induced apoptosis of head and neck squamous cell carcinoma (HNSCC) cells via Noxa-mediated mitochondrial dysregulation and ER stress.ConclusionIn addition to the elucidation of the role of IDO in the modulation of apoptosis, our study provides new insights into the molecular mechanisms of IFNγ-induced apoptosis of HNSCC cells during the course of immune therapy.

Until recently IgG autoantibodies against the basal membrane proteins BP180 und BP230 were considered to be causative in the pathogenesis of BP. However, new in vitro studies as well as data from experimental mouse models have indicated that in addition to specific IgG, also IgE antibodies against BP180 and BP230 play a role in the development of this disease. Based on these new findings, new treatment modalities of BP became possible.

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Results on blends containing different ingredients have revived the interest on the interaction parameter and crosslink density of structures that contain soft fillers. Composite blend of natural rubber and styrene butadiene rubber loaded with the percolation concentration of high abrasion furnace carbon black and different concentrations with paraffin wax were prepared. The applicability of the blends for liquid diffusion has been examined through the changes in the interaction parameter and the crosslink density at different temperatures. The transport mechanism through the vulcanized blends is governed by Fickian diffusion law at room temperatures and it becomes nonFickian at higher temperatures. The diffusion coefficients were calculated and found to have an activated behavior with temperature from which the activation energy was calculated. The change in entropy, enthalpy, and Gibbs free energy are also studied at different temperatures.

Pemphigus vulgaris is an autoimmune blistering disorder. The diagnosis is based on clinical presentation, histology, and direct and indirect immunofluorescence. Optimal treatment remains the greatest challenge. Treatment options include combinations of systemic steroids with azathioprine, mycophenolate, and cyclophosphamide. However, there is little solid data regarding the drug of choice. In our patient, the best tolerated and effective treatment was found after several therapeutic attempts.

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