Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma.

Immune checkpoint inhibition with ipilimumab has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced malignant melanoma. Local peripheral treatments (LPT), such as radiotherapy or electrochemotherapy, have been shown to modulate systemic immune responses, and preliminary data have raised the hypothesis that the combination of LPT with systemic immune checkpoint blockade might be beneficial. Clinical data from 127 consecutively treated melanoma patients at four cancer centers in Germany and Switzerland were analyzed.

Imatinib Triggers Phagolysosome Acidification and Antimicrobial Activity against Mycobacterium bovis Bacille Calmette-Guérin in Glucocorticoid-Treated Human Macrophages.

Glucocorticoids are extensively used to treat inflammatory diseases; however, their chronic intake increases the risk for mycobacterial infections. Meanwhile, the effects of glucocorticoids on innate host responses are incompletely understood. In this study, we investigated the direct effects of glucocorticoids on antimycobacterial host defense in primary human macrophages.

Vitamin D regulates cytokine patterns secreted by dendritic cells to promote differentiation of IL-22-producing T cells.

One central mechanism, by which vitamin D regulates human immune responses, is the direct modulation of dendritic cells (DCs). However, the effect of vitamin D on several key DC functions, such as the secretion of central inflammatory cytokines, remains controversial. Moreover, whether vitamin D treatment of DCs regulates their ability to promote differentiation of IL-17-/IL-22-producing T cell subsets, such as Th17 and Th22 cell, is not known.

Vitamin D every day to keep the infection away?

Within the last decade, vitamin D has emerged as a central regulator of host defense against infections. In this regard, vitamin D triggers effective antimicrobial pathways against bacterial, fungal and viral pathogens in cells of the human innate immune system. However, vitamin D also mediates potent tolerogenic effects: it is generally believed that vitamin D attenuates inflammation and acquired immunity, and thus potentially limits collateral tissue damage.

CD40 ligand and interferon-γ induce an antimicrobial response against Mycobacterium tuberculosis in human monocytes.

The ability of T cells to activate antimicrobial pathways in infected macrophages is essential to host defence against many intracellular pathogens. Here, we compared the ability of two T-cell-mediated mechanisms to trigger antimicrobial responses against Mycobacterium tuberculosis in humans, CD40 activation and the release of interferon-γ (IFN-γ). Given that IFN-γ activates a vitamin D-dependent antimicrobial response, we focused on induction of the key components of this pathway.

Sustained glutamate receptor activation down-regulates GABAB receptors by shifting the balance from recycling to lysosomal degradation.

Metabotropic GABA(B) receptors are abundantly expressed at glutamatergic synapses where they control excitability of the synapse. Here, we tested the hypothesis that glutamatergic neurotransmission may regulate GABA(B) receptors. We found that application of glutamate to cultured cortical neurons led to rapid down-regulation of GABA(B) receptors via lysosomal degradation.

Melorheostosis of the hand in a 7-year-old girl.

Melorheostosis of the hand is rare. We report a 7-year-old girl who presented with a contracture of the left hand. Diagnosis was made by conventional radiography and bone scintigraphy.