Immune Regulation News Volume 4.29 | Aug 3 2012

Multipeptide Immune Response to Cancer Vaccine IMA901 after Single-Dose Cyclophosphamide Associates with Longer Patient Survival
Researchers treated 96 human leukocyte antigen A (HLA-A)*02⁺ subjects with advanced renal cell cancer with IMA901 in two consecutive studies. In the phase I study, the T cell responses of the patients to multiple tumor-associated peptides (TUMAPs) were associated with better disease control and lower numbers of prevaccine forkhead box P3⁺ regulatory T (Treg) cells. The randomized phase II trial showed that a single dose of cyclophosphamide reduced the number of Treg cells and confirmed that immune responses to multiple TUMAPs were associated with longer overall survival. [Nat Med] Abstract

A Voltage-Gated Sodium Channel Is Essential for the Positive Selection of CD4⁺ T Cells
Researchers concluded that active voltage-gated Na⁺ channels (VGSCs) in thymocytes provide a mechanism by which a weak positive selection signal can induce the sustained Ca²⁺ signals required for CD4⁺ T cell development. [Nat Immunol] Abstract

OX40 Signaling Favors the Induction of T_H9 Cells and Airway Inflammation
Researchers found that the costimulatory receptor OX40 was a powerful inducer of T_H9 cells in vitro and T_H9 cell-dependent airway inflammation in vivo. [Nat Immunol] Abstract

Tumor-Infiltrating DCs Suppress Nucleic Acid-Mediated Innate Immune Responses through Interactions between the Receptor TIM-3 and the Alarmin HMGB1
Researchers identified the receptor TIM-3 as key in circumventing the stimulatory effects of nucleic acids in tumor immunity. Tumor-associated dendritic cells (DCs) in mouse tumors and patients with cancer had high expression of TIM-3. [Nat Immunol] Abstract

Genome-Wide Analysis Reveals Recurrent Structural Abnormalities of TP63 and Other p53-Related Genes in Peripheral T-Cell Lymphomas
The authors developed bioinformatic tools to identify chromosomal rearrangements using genome-wide, next-generation sequencing analysis of mate-pair DNA libraries and applied these tools to 16 peripheral T-cell lymphoma (PTCL) patient tissue samples and six PTCL cell lines. Thirteen recurrent abnormalities were identified, of which five involved p53-related genes. [Blood] Abstract | Press Release

Neogenesis of Lymphoid Structures and Antibody Responses Occur in Human Melanoma Metastases
Researchers observed ectopic lymphoid structures, defined as lymphoid follicles comprising clusters of B lymphocytes and follicular dendritic cells (DCs), associated with high endothelial venules and clusters of T cells and mature DCs, in seven of 29 cutaneous metastases from melanoma patients. [Cancer Res]
Abstract | Press Release

Inhibition of LTi Cell Development by CD25 Blockade Is Associated with Decreased Intrathecal Inflammation in Multiple Sclerosis
The number of circulating retinoic acid receptor-related orphan receptor γt-positive innate lymphoid cells (ILCs), which include lymphoid tissue inducer (LTi) cells, was found to be elevated in untreated multiple sclerosis patients compared to healthy subjects. Daclizumab therapy not only decreased numbers of ILCs but also modified their phenotype away from LTi cells and toward a natural killer cell lineage. [Sci Transl Med] Abstract | Press Release

A Role for Mucosal IL-22 Production and Th22 Cells in HIV-Associated Mucosal Immunopathogenesis
Researchers found that sigmoid interleukin-22 (IL-22)-producing T cells and Th22 cells were dramatically depleted during chronic HIV infection, epithelial integrity was compromised, and microbial translocation was increased. These alterations were reversed after long-term antiretroviral therapy. [Mucosal Immunol] Abstract

Decoding the Regulation of Mast Cell Exocytosis by Networks of Rab GTPases
Researchers report on the identification of 30 Rabs as regulators of mast cell exocytosis, the involvement of 26 of which has therefore not been recognized. [J Immunol] Abstract | Press Release

Inhibition of Mechanistic Target of Rapamycin Promotes Dendritic Cell Activation and Enhances Therapeutic Autologous Vaccination in Mice
Researchers showed that brief exposure to inhibitors of mechanistic target of rapamycin in dendritic cells during the period that they are responding to TLR agonists makes them particularly potent activators of naive CD8⁺ T cells and able to enhance control of B16 melanoma in a therapeutic autologous vaccination model in the mouse. [J Immunol] Abstract | Press Release

ABL Awarded NIH Contract to Fund up to $102 Million in Biologics Manufacturing and Characterization Services
Advanced BioScience Laboratories, Inc. (ABL) announced the award of a contract to provide the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) with preclinical development and cGMP manufacturing support for multiple vaccine and biologic products identified by NIAID Program staff. [Advanced Bioscience Laboratories, Inc.] Press Release

Future Fellows Win $2.1 Million for Infectious Disease Research
Walter and Eliza Hall Institute researchers Dr. Melissa Call, Dr. Wai-Hong Tham and Dr. Chris Tonkin were three of 209 Australian and international researchers awarded Australian Research Council Future Fellowships. They will each receive $700,000 over five years from the program to fund their research into infectious diseases and the immune response to infection. [Walter and Eliza Hall Institute of Medical Research] Press Release

U.S. Federal Court Says Stem Cell Treatments Are Drugs
A U.S. federal court has found that a stem cell therapy offered by a Colorado clinic meets the definition of a regulated drug. The ruling could spur a U.S. Food and Drug Administration crackdown on other clinics offering untested adult stem cell treatments in the United States. [U.S. District Court for the District of Columbia, United States] Press Release

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NEW 26^th Annual Canadian Society for Immunology (CSI) Conference
April 5-8, 2013
Whistler, Canada

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