Volume 5.08 | Mar 1

Immune Regulation News 5.08 March 1, 2013
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY

Scientists Identify Bone-Marrow Environment that Helps Fight Infection
Research has deepened the understanding of the environment within bone marrow that nurtures stem cells, this time identifying the biological setting for specialized blood-forming cells that produce the infection-fighting white blood cells known as T cells and B cells. The research found that cells called early lymphoid progenitors, which are responsible for producing T cells and B cells, thrive in an environment known as an osteoblastic niche. [Press release from The University of Texas Southwestern Medical Center discussing online prepublication in Nature] Press Release | Abstract

Free Nature Reviews Immunology Poster: The Immune Response to HIV

PUBLICATIONS (Ranked by impact factor of the journal)

Quantitative Assessment of T Cell Repertoire Recovery after Hematopoietic Stem Cell Transplantation
Researchers combined 5′ rapid amplification of complementary DNA ends PCR with deep sequencing to quantify T cell receptor (TCR) diversity in 28 recipients of allogeneic hematopoietic stem cell transplantation using a single oligonucleotide pair. After 6 months, cord blood-graft recipients approximated the TCR diversity of healthy individuals, whereas recipients of T cell-depleted peripheral-blood stem cell grafts had 28-fold and 14-fold lower CD4+ and CD8+ T cell diversities, respectively. After 12 months, these deficiencies had improved for the CD4+ but not the CD8+ T cell compartment. [Nat Med] Abstract

Murine Dendritic Cell Rapamycin-Resistant and Rictor-Independent mTOR Controls IL-10, B7-H1 and Regulatory T Cell Induction
Investigators defined an immunoregulatory pathway where rapamycin (RAPA)-sensitive mammalian target of rapamycin complex 1 (mTORC1) in dendritic cells promotes effector T cell expansion and RAPA-insensitive mTORC1 restrains regulatory T cell induction. [Blood] Abstract

Foxp3+ T-Regulatory Cells Require DNA Methyltransferase 1 Expression to Prevent Development of Lethal Autoimmunity
Researchers found that DNA methyltransferase 1 is necessary for maintenance of the core gene program underlying T-regulatory (Treg) development and function, and its deletion within the Treg lineage leads to lethal autoimmunity. [Blood] Abstract

Ex Vivo Activation of CD56+ Immune Cells that Eradicate Neuroblastoma
Despite the use of intensive contemporary multimodal therapy, the overall survival of patients with high-risk neuroblastoma is still less than 50%. Therefore, immunotherapy without cross-resistance and overlapping toxicity has been proposed. Scientists report the development of a novel strategy to specifically activate and expand human CD56+ natural killer immune cells from normal donors and neuroblastoma patients. [Cancer Res] Abstract

Epithelial-to-Mesenchymal Transition and Autophagy Induction in Breast Carcinoma Promote Escape from T Cell-Mediated Lysis
Epithelial-to-mesenchymal transition mediates cancer cell invasion, metastasis and drug resistance, but its impact on immune surveillance has not been explored. Researchers investigated the functional consequences of this mode of epithelial cell plasticity on targeted cell lysis by cytotoxic T lymphocytes. [Cancer Res] Abstract

Transferred WT1-Reactive CD8+ T Cells Can Mediate Antileukemic Activity and Persist in Post-Transplant Patients
HLA-A*0201-restricted Wilms tumor antigen 1 (WT1)-specific donor-derived CD8+ cytotoxic T cell (CTL) clones were administered after hematopoietic cell transplantation to 11 relapsed or high-risk leukemia patients without evidence of on-target toxicity. The last four treated patients received CTL clones generated with exposure to interleukin-21 (IL-21) to prolong in vivo CTL survival, because IL-21 can limit terminal differentiation of antigen-specific T cells generated in vitro. [Sci Transl Med] Abstract | Press Release

CD19+CD24hiCD38hi B Cells Maintain Regulatory T Cells While Limiting TH1 and TH17 Differentiation
Results suggest that in patients with active rheumatoid arthritis, CD19+CD24hiCD38hi B cells with regulatory function may fail to prevent the development of autoreactive responses and inflammation, leading to autoimmunity. [Sci Transl Med] Abstract

Cetuximab-Activated Natural Killer (NK) and Dendritic Cells (DC) Collaborate to Trigger Tumor Antigen-Specific T Cell Immunity in Head and Neck Cancer Patients
Researchers concluded that cetuximab-activated NK cells promote DC maturation and CD8+ T cell priming, leading to tumor antigen-spreading and Th1 cytokine release through ‘NK-DC cross-talk.’ FcγRIIIa polymorphism did not predict clinical response to cetuximab, but was necessary for NK-DC interaction and monoclonal antibody induced cross-presentation. [Clin Cancer Res] Abstract

Constitutively CD40-Activated B Cells Regulate CD8 T Cell Inflammatory Response by IL-10 Induction
Using a mouse model in which B cells express a CD40 ligand (CD40L) transgene (CD40LTg) and receive autocrine CD40/CD40L signaling, researchers showed that CD40LTg B cells stimulated memory-like CD4 and CD8 T cells to express IL-10. This IL-10 expression by CD8 T cells was dependent on IFN-I and programmed cell death protein 1, and was critical for CD8 T cells to counterregulate their overactivation. [J Immunol] Abstract

Interferon-Gamma and Granulocyte/Monocyte Colony-Stimulating Factor Production by Natural Killer Cells Involves Different Signaling Pathways and the Adaptor Stimulator of Interferon Genes (STING)
Scientists previously showed that murine spleen natural killer (NK) cells express toll-like receptor 9 (TLR9) intracellularly and respond to CpG oligodeoxynucleotide (CpG-ODN) by producing interferon-gamma (IFN-γ) and granulocyte-macrophage colony stimulating factor (GM-CSF). However, to get such production the presence of accessory cytokines (such as IL-15 and IL-18) was required, whereas CpG-ODN or accessory cytokines alone did not induce IFN-γ or GM-CSF. The authors showed that TLR9 overlaps with the Golgi apparatus in NK cells. [J Biol Chem] Abstract | Full Article

Learn more about the new smartphone app for human blood cell frequencies

REVIEWS

Neutrophil Recruitment and Function in Health and Inflammation
Researchers discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. They focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, they explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites. [Nat Rev Immunol] Abstract

Regulation of Nuclear Factor-κB in Autoimmunity
This review focuses on recent progress regarding nuclear factor (NF)-κB regulation and its association with autoimmunity. [Trends Immunol] Abstract

INDUSTRY NEWS

NW Bio Takes Next Steps in Moving Forward with Its Phase III Brain Cancer Trial in Europe
Northwest Biotherapeutics (NW Bio) announced that, building upon nearly three years of  manufacturing development, regulatory processes and  clinical preparations in Europe, the Company has named a leading international contract research organization to manage the Company’s 312-patient Phase III clinical trial for glioblastoma multiforme brain cancer in Europe. The Company has a broad platform technology for DCVax® dendritic cell-based vaccines. [Northwest Biotherapeutics] Press Release

Sernova and Centre for Commercialization of Regenerative Medicine Partner to Treat Chronic Diseases
The Centre for Commercialization of Regenerative Medicine (CCRM) announced the addition of Sernova Corp. to its member-based industry consortium. Sernova’s combination of immuno-protective technology and therapeutic cells for the treatment of chronic diseases advances CCRM’s goal of developing innovative cell-based products. [Centre for Commercialization of Regenerative Medicine] Press Release

Ignyta Signs Rheumatoid Arthritis Research Collaboration with Leiden University Medical Center
Ignyta, Inc. announced a collaboration with Leiden University Medical Center to assess the epigenetic signatures of patients with early synovitis and rheumatoid arthritis. [Business Wire] Press Release

POLICY NEWS

Expanding Public Access to the Results of Federally Funded Research
In a policy memorandum, Office of Science and Technology Policy Director John Holdren has directed Federal agencies with more than $100 million in R&D expenditures to develop plans to make the published results of federally funded research freely available to the public within one year of publication and requiring researchers to better account for and manage the digital data resulting from federally funded scientific research. [Office of Science and Technology Policy, The White House, United States] Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS
NEW 3rd ESOT Basic Science Meeting & 13th TTS Basic Science Symposium
November 7-9, 2013
Paris, France

Visit our events page to see a complete list of events in the immune regulation community.
JOB OPPORTUNITIES

Postdoctoral Fellow – Transcriptional Regulation in CD8 T Lymphocytes (Université Libre de Bruxelles – Institute for Medical Immunology)

Faculty Positions – Cancer Inflammation and Tolerance (Georgia Health Sciences University Cancer Center)

Postdoctoral Position – IL-17 and Inflammation Research (Hospices Civils de Lyon)

PhD Candidate – Immunoregulatory Properties of Stromal and Immune Cells (University of Saarland, Internal Medicine II)

Postdoctoral Position – NK/T Cells (The Ohio State University – Comprehensive Cancer Center)

Research Specialist – Tolerance and Antirejection Techniques in Transplantation (University of Chicago)

Postdoctoral Position – Immunology (Institut Pasteur)

Postdoctoral Fellow – Immunotherapeutics in Childhood Cancer (Perelman School of Medicine at the University of Pennsylvania)


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