Volume 5.22 | Jun 14

Immune Regulation News 5.22 June 14, 2013
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Endocytosis and Recycling of Immune Complexes by Follicular Dendritic Cells Enhances B Cell Antigen Binding and Activation
The authors found that follicular dendritic cells acquired complement-coated immune complexes (ICs) from noncognate B cells via complement receptors 1 and 2 (CD35 and CD21, respectively) and rapidly internalized them by an actin-dependent pathway. ICs were retained intact within a nondegradative cycling compartment and were displayed periodically on the cell surface where they were accessible to antigen-specific B cells. [Immunity] Abstract | Graphical Abstract

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Effector-Like CD8+ T Cells in the Memory Population Mediate Potent Protective Immunity
Researchers investigated the protective capacities of CD8+ T cell subsets present at the memory stage of the immune response. They showed that a population of CD8+ T cells bearing markers associated with effector cells (KLRG1hi, CD27lo, T-bethi, Eomeslo) persisted to the memory phase and provided optimal control of Listeria monocytogenes and vaccinia virus, despite weak recall proliferative responses. [Immunity] Abstract

ROS Play a Critical Role in the Differentiation of Alternatively Activated Macrophages and the Occurrence of Tumor-Associated Macrophages
Scientists report that reactive oxygen species (ROS) production is critical for macrophage differentiation and that inhibition of superoxide (O2-) production specifically blocks the differentiation of alternatively activated macrophages. They found that when monocytes are triggered to differentiate, O2- is generated and is needed for the biphasic ERK activation, which is critical for macrophage differentiation. [Cell Res] Full Article

IL-18-Primed Helper NK Cells Collaborate with Dendritic Cells to Promote Recruitment of Effector CD8+ T Cells to the Tumor Microenvironment
The authors showed that IL-18-primed ‘helper’ natural killer (NK) cells produce high levels of the immature dendritic cell (iDC)-attracting chemokines CCL3 and CCL4 upon exposure to tumor cells or the additional inflammatory signals IFNα, IL-15, IL-12, or IL-2. These ‘helper’ NK cells potently attract iDCs in a CCR5-dependent mechanism and induce high DC production of CXCR3 and CCR5 ligands (CXCL9, CXCL10, and CCL5), facilitating the subsequent recruitment of type-1 effector CD8+ T cells. [Cancer Res] Abstract

Basophils Control T-Cell Responses and Limit Disease Activity in Experimental Murine Colitis
Using the colitis model of adoptive transfer of CD4+ CD62L+ T cells into lymphopenic hosts, investigators have analyzed how basophils regulate T-cell responses and modulate disease activity. [Mucosal Immunol] Abstract

B Cell-Intrinsic TLR7 Signaling Is Required for Optimal B Cell Responses during Chronic Viral Infection
Investigators demonstrated that deficiency of TLR7 in B cells alone is sufficient to significantly impact Ab responses in mice during chronic viral infection. This effect was independent of T follicular helper cells and resulted in a loss of plasma cells generated later, but not early, in the response. [J Immunol] Abstract

B7-1/B7-2 Blockade Overrides the Activation of Protective CD8 T Cells Stimulated in the Absence of Foxp3+ Regulatory T Cells
Researchers showed that the elimination of regulatory T cell (Treg) suppression does not bypass the requirement for positive B7-1 (CD80)/B7-2 (CD86) costimulation. The expansion, IFN-γ cytokine production, cytolytic, and protective features of antigen-specific CD8 T cells stimulated with purified cognate peptide in Treg-ablated mice were each neutralized effectively by CTLA-4-Ig that blocks B7-1/B7-2. [J Leukoc Biol] Abstract

Bleomycin Exerts Ambivalent Antitumor Immune Effect by Triggering Both Immunogenic Cell Death and Proliferation of Regulatory T Cells
The authors observed that bleomycin (BLM) induces immunogenic cell death. In particular, BLM is able to induce ROS-mediated reticulum stress and autophagy, which result in the surface exposure of chaperones, including calreticulin and ERp57, and liberation of HMBG1 and ATP. BLM induces anti-tumor immunity which relies on calreticulin, CD8+ T cells and interferon-γ. They also find that, in addition to its capacity to trigger immunogenic cell death, BLM induces expansion of Foxp3+ regulatory T cells via its capacity to induce transforming growth factor beta secretion by tumor cells. [PLoS One] Full Article

Placenta-Derived gp96 as a Multivalent Prophylactic Cancer Vaccine
A major challenge for designing prophylactic cancer vaccines is to define immunogenic and safe cancer antigens. Given the striking similarity of antigen expression patterns between cancer and embryonic tissues, they defined a prototype strategy of using placenta-derived heat shock protein gp96, which induces prophylactic anti-tumor T cell responses. [Sci Rep] Full Article

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On Guard: Coronin Proteins in Innate and Adaptive Immunity
Coronins are involved in processes as diverse as pathogen survival in phagocytes and homeostatic T cell signaling. Notably, in both mice and humans, coronin mutations are associated with immune deficiencies and resistance to autoimmunity. The authors review what is currently known about these conserved molecules and discuss a potential common mechanism that underlies their diverse activities, which seem to involve cytoskeletal interactions as well as calcium-calcineurin signaling. [Nat Rev Immunol] Abstract

The Relationship between Metabolism and the Autophagy Machinery during the Innate Immune Response
The innate immune response is shaped by multiple factors, including both traditional autophagy and LC3-associated phagocytosis (LAP). As the autophagic machinery is engaged during times of nutrient stress, arising from scarcity or pathogens, the authors examine how autophagy, specifically LAP, and cellular metabolism together influence macrophage function and the innate immune response. [Cell Metab] Abstract

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Immunomedics Reports that UCB Announces New Results from Phase IIb Open-Label Extension Study Evaluating the Long-Term Effects of Epratuzumab in SLE
Immunomedics, Inc. reported that UCB (Euronext Brussels: UCB), announced new data from an open-label extension of the EMBLEM™ phase IIb study evaluating the long-term effects of epratuzumab treatment in adult patients with moderate-to-severe systemic lupus erythematosus (SLE). [Press release from Immunomedics, Inc. discussing research presented at the European League Against Rheumatism 2013 Congress, Madrid] Press Release

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Phase I Trial Uses Enhanced T Cells to Treat Neuroblastoma
A phase I clinical trial at Baylor College of Medicine and Texas Children’s Cancer Center using an immunotherapy approach to treat neuroblastoma has received support from the nonprofit organization Solving Kids’ Cancer. The organization provided $153,000 for the trial, which will start this summer. Dr. Chrystal Louis, assistant professor of pediatrics – hematology/oncology at Baylor College of Medicine, serves as principal investigator. [Baylor College of Medicine] Press Release

NW Bio Has Initiated Its Dcvax®-Direct Phase I/II Trial for All Solid Tumor Cancers
Northwest Biotherapeutics (NW Bio), a biotechnology company developing non-toxic DCVax® personalized immune therapies for solid tumor cancers, announced that its 60-patient Phase I/II clinical trial of DCVax-Direct for all inoperable solid tumor cancers has been initiated at The University of Texas MD Anderson Cancer Center in Houston, Texas. [Northwest Biotherapeutics] Press Release

Generex Announces Interview of MD Anderson’s Dr. Elizabeth Mittendorf, Principal Investigator on Company’s AE37 Phase IIb Breast Cancer Efficacy Trial
Generex Biotechnology Corporation announced an interview given by Dr. Elizabeth Mittendorf, M.D., Ph.D.  Dr. Mittendorf is the Principal Investigator of the Company’s AE37 clinical trial to test the ability of the novel immunotherapeutic agent to prevent relapse in patients who have had HER2-expressing breast cancer, the largest Phase IIb peptide clinical trial conducted to date. [Generex Biotechnology Corporation]
Press Release

Yale’s Ruslan Medzhitov Wins Inaugural Award for Immunology
The Else Kröner-Fresenius-Foundation has awarded its inaugural international prize in immunology to renowned Yale immunobiologist Ruslan Medzhitov. The prize of four million euros was presented by the Federal Research Minister of Germany, Johanna Wanka, in a ceremony held at the German Historical Museum in Berlin. [Yale University] Press Release


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NEW 39th American Society for Histocompatibility and Immunogenetics (ASHI) Annual Meeting
November 17-21, 2013
Chicago, United States

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NEW Postdoctoral Fellowship – Immune Regulation by Extracellular Matrix Proteins (Johns Hopkins University – School of Medicine)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

PhD Studentship – Cancer and Chronic Inflammation (TU Dresden – Institute of Immunology)

Postdoctoral Position – Immunological Modeling (Université catholique de Louvain (UCL))

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Research Associates – Immune Response (NCSR Demokritos, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety)

Postdoctoral Position – Mechanistic Studies in Immune Responses (Medical University of Vienna)

Postdoctoral Researcher – Innate Immunity (Massachusetts General Hospital / Harvard Medical School)

Postdoctoral Fellowship – Tumor Immunology (Northwestern University – Robert H Lurie Comprehensive Cancer Center)

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