Human Immunology News Volume 2.18 | May 13 2014

Intravenous Immunoglobulin Treatment in Humans Suppresses Dendritic Cell Function via Stimulation of IL-4 and IL-13 Production
Researchers showed that i.v. Ig (IVIg) in patients results in increases in plasma levels of IL-33, IL-4, and IL-13 and that increments in IL-33 levels correlate with rises in plasma IL-4 and IL-13 levels. Strikingly, no upregulation of FcγRIIb expression was found, but instead a decreased expression of the activating FcγRIIa on circulating myeloid dendritic cells after high-dose, but not after low-dose, IVIg treatment. [J Immunol] Abstract

Dectin-1 Pathway Activates Robust Autophagy-Dependent Unconventional Protein Secretion in Human Macrophages
Scientists used a systems biology approach to provide the first comprehensive characterization of the secretome and associated intracellular signaling pathways involved in activation of dectin-1/Syk in human macrophages. [J Immunol] Abstract

Direct T Cell-Tumor Interaction Triggers T_H1 Phenotype Activation through the Modification of the Mesenchymal Stromal Cells Transcriptional Program
Tumor-activated tumor infiltrating lymphocytes induced T_H1 phenotype change in mesenchymal stromal cells that is qualitatively similar to the previously described immunologic constant of rejection signature observed during immune-mediated, tissue-specific destruction. This response may be responsible for the in loco amplification of antigen-specific anti-cancer immune response. [Br J Cancer] Full Article

Yeast Modulation of Human Dendritic Cell Cytokine Secretion: An In Vitro Study
Researchers evaluated 170 yeast strains representing 75 diverse species for modulation of inflammatory cytokine secretion by human dendritic cells (DCs) in vitro, as compared to cytokine responses induced by a Saccharomyces boulardii reference strain with probiotic properties documented in clinical trials. Furthermore, they investigated whether cytokine inducing interactions between yeasts and human DCs are dependent upon yeast viability or rather a product of membrane interactions regardless of yeast metabolic function. [PLoS One] Full Article

Hepatitis C Virus Core Protein Inhibits Interferon Production by a Human Plasmacytoid Dendritic Cell Line and Dysregulates Interferon Regulatory Factor-7 and Signal Transducer and Activator of Transcription (STAT) 1 Protein Expression
Investigators defined how extracellular HCV core protein (Core) modulates pattern recognition receptor signaling in plasmacytoid dendritic cells (pDCs). Type I and III interferon expression and production following exposure to recombinant Core or β-galactosidase was assessed in human GEN2.2 cells, a pDC cell line. [PLoS One]
Full Article

Ovarian Tumor-Associated MicroRNA-20a Decreases Natural Killer Cell Cytotoxicity by Downregulating MICA/B Expression
Investigators found that microRNA-20a binds directly to the 3′-untranslated region of MICA/B mRNA, resulting in its degradation and reducing its protein levels on the plasma membrane. Reduction of membrane-bound MICA/B proteins, which are ligands of the natural killer group 2 member D receptor found on natural killer cells, γδ⁺ T cells and CD8⁺ T cells, allows tumor cells to evade immune-mediated killing. [Cell Mol Immunol] Abstract

High-Dose Interleukin-2 Therapy for Metastatic Renal Cell Carcinoma: A Contemporary Experience
Researchers presented their experience of high-dose interleukin-2 in a high-volume National Cancer Institute-designated center for patients with metastatic renal cell carcinoma. [Urology] Abstract | Press Release

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Medical College of Wisconsin Receives Grant from National Cancer Institute to Develop Novel Cellular Immunotherapy
The Medical College of Wisconsin has received a five-year, $1.6 million grant from the National Institutes of Health’s National Cancer Institute to support development of novel immune cell-based therapies to cancer. [Medical College of Wisconsin] Press Release

AstraZeneca Initiates Phase III Immunotherapy Study for MEDI4736 in Patients with Lung Cancer
AstraZeneca announced the start of the Phase III program for MEDI4736, an immunotherapy in development for the treatment of non-small cell lung cancer and other cancers. [AstraZeneca] Press Release

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