Immune Regulation News Volume 7.28 | Jul 31 2015

Out-of-Sequence Signal 3 Paralyzes Primary CD4⁺ T-Cell-Dependent Immunity
Researchers showed that during strong stimulation, a profound suppression of primary CD4⁺ T-cell-mediated immune responses ensued and was observed across preclinical models and patients undergoing high-dose interleukin-2 therapy. [Immunity] Abstract | Graphical Abstract

LEF-1 and TCF-1 Orchestrate T_FH Differentiation by Regulating Differentiation Circuits Upstream of the Transcriptional Repressor Bcl6
The authors report that selective loss of Lef1 or Tcf7 (which encode the transcription factor LEF-1 or TCF-1, respectively) resulted in follicular helper T (T_FH) cell defects, while deletion of both Lef1 and Tcf7 severely impaired the differentiation of T_FH cells and the formation of germinal centers. Forced expression of LEF-1 enhanced T_FH differentiation. [Nat Immunol] Abstract | Press Release

Intestinal Inhibition of Atg7 Prevents Tumor Initiation through a Microbiome-Influenced Immune Response and Suppresses Tumor Growth
Investigators showed that autophagy is activated in the intestinal epithelium in murine and human colorectal cancer and that the conditional inactivation of Atg7 in intestinal epithelial cells inhibits the formation of pre-cancerous lesions in Apc^+/− mice by enhancing anti-tumor responses. The antibody-mediated depletion of CD8⁺ T cells showed that these cells are essential for the anti-tumoral responses mediated by the inhibition of autophagy. [Nat Cell Biol] Abstract

Intestinal CD169⁺ Macrophages Initiate Mucosal Inflammation by Secreting CCL8 that Recruits Inflammatory Monocytes
Following mucosal injury, the CD169⁺ macrophages recruited inflammatory monocytes by secreting CCL8. Selective depletion of CD169⁺ macrophages or administration of neutralizing anti-CCL8 antibody ameliorated the symptoms of experimentally induced colitis in mice. [Nat Commun] Full Article

Active Suppression of Intestinal CD4⁺TCRαβ⁺ T-Lymphocyte Maturation during the Postnatal Period
Scientists showed that shortly after birth, CD4 T cells populate preformed lymphoid structures in the small intestine and quickly acquire a distinct transcriptional profile. T-cell recruitment is independent of microbial colonization and innate or adaptive immune stimulation but requires β7 integrin expression. [Nat Commun] Full Article

Spontaneous Retrotransposon Insertion into TNF 3′UTR Causes Heart Valve Disease and Chronic Polyarthritis
Investigators studied a new spontaneous mutation that causes severe polyarthritis in bone phenotype spontaneous mutation 1 mice. They found that several members of a family of RNA-binding, CCCH-containing zinc-finger proteins control tumor necrosis factor (TNF) expression through its 3′ untranslated region (3′UTR), and identified a previously unidentified regulatory element in the UTR. [Proc Natl Acad Sci USA]
Abstract | Full Article | Press Release

Interferon-Beta Therapy of Multiple Sclerosis Patients Improves the Responsiveness of T Cells for Immune Suppression by Regulatory T Cells
Researchers investigated T cell function in multiple sclerosis patients before and after interferon-beta therapy. They compared cytokine profile, responsiveness for Treg-mediated suppression ex vivo and evaluated reactivity of T cells in vivo using a humanized mouse model. [Int J Mol Sci] Full Article

Modulation of Dendritic Cell Function by the Radiation-Mediated Secretory Protein γ-Synuclein
Scientists investigated whether radiation-induced, tumor-derived γ-synuclein (SNCG) can influence dendritic cell (DC) function in immune systems. The ability of SNCG-treated DCs to influence T cells was also examined by coculturing with T cells. [Cell Death Discov] Full Article

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Combination Cancer Immunotherapy and New Immunomodulatory Targets
The authors discuss the leading drug targets that are expressed on tumor cells and in the tumor microenvironment that allow enhancement of the antitumor immune response. [Nat Rev Drug Discov] Abstract

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Merck Enhances Immuno-Oncology Portfolio with Acquisition of cCAM Biotherapeutics
Merck and cCAM Biotherapeutics announced that the companies have signed a definitive agreement under which Merck will acquire cCAM Biotherapeutics, a privately held biopharmaceutical company focused on the discovery and development of novel cancer immunotherapies. [Merck & Co., Inc.] Press Release

Moffitt Cancer Center Teams Up with MD Anderson to Discover, Test Novel Agents to Prevent Cancer
Moffitt Cancer Center has joined MD Anderson’s National Cancer Institute (NCI) Phase 0/I/II Cancer Prevention Clinical Chemoprevention Trials Consortia. Sponsored by the NCI’s Division of Cancer Prevention, the consortia conducts early clinical development of promising new preventive agents through its Phase 0/I/II Cancer Prevention Clinical Trials Program. [Moffitt Cancer Center (Newswise, Inc.)] Press Release

Bavarian Nordic Announces Initiation of NCI-sponsored Phase II Study of PROSTVAC in Patients with Localized Prostate Cancer
Bavarian Nordic A/S announced that the first patient has been enrolled in a new Phase II clinical study of PROSTVAC, the company’s active prostate cancer immunotherapy candidate. [Bavarian Nordic A/S] Press Release

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NEW Harry Eagle Scholar Awards for Postdoctoral Candidates (Albert Einstein College of Medicine of Yeshiva University)

NEW Postdoctoral Positions – Cancer Research (Rutgers University)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Scientific Marketing Specialist – Immunology (STEMCELL Technologies Inc.)

Research Associate – Cell Biology (Editas Medicine)

Senior Research Associate – CRISPR-Based Therapeutics (Editas Medicine)

Research Assistant – Immunotherapy for HIV Infection (California Institute of Technology)

Postdoctoral Position – Translational Immunology (University of Utah School of Medicine)

PhD Studentship – Veterinary and Animal Sciences (University of Milan)

Postdoctoral Researcher – Tumorigenesis and Immune Response (Nationwide Children Hospital-Ohio)

Senior Scientist – Immunology (Valera LLC)

Postdoctoral Fellow – Antibody Engineering/Immuno-Oncology (California Institute for Biomedical Research)

Associate Director/Director – Immunology (Valera)

Postdoctoral Fellow – Immune Reconstitution in Hematopoietic Stem Cell Transplantation (Stanford University)

Assistant Professor – Immunology (Northwestern University)

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