Immune Regulation News Volume 6.47 | Dec 12 2014

B Cell Super-Enhancers and Regulatory Clusters Recruit AID Tumorigenic Activity
Investigators studied activation-induced cytidine deaminase (AID)-mediated lesions in the context of nuclear architecture and the B cell regulome. They show that AID targets are not randomly distributed across the genome but are predominantly grouped within super-enhancers and regulatory clusters. [Cell]
Abstract | Graphical Abstract

Neutrophils Scan for Activated Platelets to Initiate Inflammation
Investigators report that neutrophil polarization within activated venules served to organize a protruding domain that engaged activated platelets present in the bloodstream. The selectin ligand PSGL-1 transduced signals emanating from these interactions, resulting in the redistribution of receptors that drive neutrophil migration. [Science] Abstract

Interleukin-10-Producing Plasmablasts Exert Regulatory Function in Autoimmune Inflammation
Researchers demonstrate that plasmablasts in the draining lymph nodes serve as interleukin-10 (IL-10) producers to limit autoimmune inflammation and emphasize the importance of plasmablasts as IL-10-producing regulatory B cells. [Immunity] Abstract | Graphical Abstract

Myeloid-Derived Suppressor Activity Is Mediated by Monocytic Lineages Maintained by Continuous Inhibition of Extrinsic and Intrinsic Death Pathways
Using genetic manipulation of cell death pathways, investigators found the monocytic suppressor-cell subset, but not the granulocytic subset, requires continuous c-FLIP expression to prevent caspase-8-dependent, RIPK3-independent cell death. [Immunity] Abstract | Graphical Abstract

Redox and Src Family Kinase Signaling Control Leukocyte Wound Attraction and Neutrophil Reverse Migration
Scientists studied the interactions between macrophages and neutrophils in response to tissue damage in zebrafish and found that macrophages contact neutrophils and induce resolution via neutrophil reverse migration. [J Cell Biol] Abstract | Editorial

Dermal V^γ4⁺γδ T Cells Possess a Migratory Potency to the Draining Lymph Nodes and Modulate CD8⁺ T Cell Activity Through Tnf-α Production
A recent study demonstrated that γδ T cells and cutaneous dendritic cells migrate from the skin to the draining lymph nodes (LNs). However, it remains unclear whether they regulate the antigen-specific immune response within the LNs. Researchers investigated their properties and role in the LNs using the Mycobacterium bovis bacille Calmette-Guérin infection model. [J Invest Dermatol] Abstract

Anti-CD33 Chimeric Antigen Receptor Targeting Of Acute Myeloid Leukemia
Researchers generated a second generation CD33-specific chimeric antigen receptor capable of redirecting cytolytic effector T cells against leukemic cells. The CD33-redirected T cells were effective in vivo, preventing leukemia development after prophylactic administration and delaying the progression of established disease in mice. [Haematologica] Abstract | Full Article

Homotypic NK Cell-to-Cell Communication Controls Cytokine Responsiveness of Innate Immune NK Cells
Using a specialized cell-laden microwell approach, scientists discovered that NK cells experiencing constant NK-to-NK contact exhibit a synergistic increase in activation status, cell proliferation, and anti-tumor function in response to IL-2 or IL-15. [Sci Rep] Full Article

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Immune Function Marker Does Not Predict Benefit of Trastuzumab in HER-2⁺ Breast Cancer Patients
A marker of immune function that predicts for better outcomes in patients treated with chemotherapy for triple negative breast cancer—the quantity of tumor-infiltrating lymphocytes (S-TILs) in a biopsy—appears irrelevant when trastuzumab is used. [Press release from Mayo Clinic discussing research presented at the 2014 San Antonio Breast Cancer Symposium (SABCS)] Press Release

MacroGenics Announces Presentation of Pre-Clinical Data on New DART^® Candidate MGD011
MacroGenics, Inc. announced the presentation of pre-clinical data for MGD011, a humanized CD19 x CD3 Dual-Affinity Re-Targeting (DART^®) protein. [Press release from MacroGenics Inc. discussing research presented at the 56^th Annual Meeting of the American Society of Hematology (ASH), San Francisco] Press Release

Immunotherapy Shows Clinical Benefit in Relapsed Transplant Recipients
A multicenter Phase I trial of the immune checkpoint blocker ipilimumab found clinical benefit in nearly half of blood cancer patients who had relapsed following allogeneic stem cell transplantation. [Press release from Dana-Farber Cancer Institute discussing research presented at the 56^th Annual Meeting of the American Society of Hematology (ASH), San Francisco] Press Release

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International Breast Cancer Study Group, Breast International Group and Merck Announce Opening of International PANACEA Study of Patients with HER2⁺ Breast Cancer
The PANACEA study will investigate the use of pembrolizumab (KEYTRUDA^®) in combination with trastuzumab to evaluate whether the addition of an anti-PD-1 therapy can reverse trastuzumab resistance in patients with HER2⁺ breast cancer whose cancer has spread while on trastuzumab therapy. [Merck & Co., Inc.] Press Release

Immunovaccine Gets FDA Fast Track Status for DPX-Survivac for Ovarian Cancer
Immunovaccine Inc. announced that DPX-Survivac has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) as maintenance therapy in subjects with advanced ovarian, fallopian tube, and peritoneal cancer who have no measureable disease following surgery and front-line platinum/taxane chemotherapy to improve their progression-free survival. [Immunovaccine Inc.] Press Release

FDA Grants Cytori Conditional Approval for a U.S. Pivotal Clinical Trial in Scleroderma
Cytori Therapeutics, Inc. announced that the U.S. Food and Drug Administration has granted conditional approval for an Investigational Device Exemption for a pivotal clinical trial, named the ‘STAR’ trial, to evaluate Cytori Cell Therapy™ as a potential treatment for impaired hand function in scleroderma. [Cytori Therapeutics, Inc.] Press Release

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NEW Postdoctoral Position – Immunology (Inserm)

Postdoctoral Research Associate – Immunology (University of Edinburgh)

Postdoctoral Position – Immunology (Centre Léon Bérard)

Postdoctoral Position – Mucosal Immunology (Karolinska Institute)

Research Associate – B Cell Biology (King’s College London)

Researcher – Antitumor Immune Cell Response (ACAVI)

Postdoctoral Fellow – Genetic and Epigenetic Regulatory Networks in Protective Immune Responses (Washington University School of Medicine)

PhD Studentship – Cancer Immunology (Cardiff University)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

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