Volume 4.18 | May 10

Human Immunology News 4.18 May 10, 2016
Human Immunology News
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Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells
Investigators report gene regulatory circuitries for four human innate lymphoid cell (ILC)-T helper (Th) counterparts derived from mucosal environments, revealing that each ILC subset diverges as a distinct lineage from Th and circulating natural killer cells but shares circuitry devoted to functional polarization with their Th counterparts. [Cell] Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
miR-424(322) Reverses Chemoresistance via T-Cell Immune Response Activation by Blocking the PD-L1 Immune Checkpoint
Scientists demonstrated that miR-424(322) regulates the PD-L1/PD-1 and CD80/CTLA-4 pathways in chemoresistant ovarian cancer. miR-424(322) was inversely correlated with PD-L1, PD-1, CD80 and CTLA-4 expression. [Nat Commun] Full Article

NLRC5/MHC Class I Transactivator Is a Target for Immune Evasion in Cancer
Scientists showed that the MHC class I transactivation pathway mediated by NLRC5 (NOD-like receptor family, caspase recruitment domain containing 5) constitutes a target for cancer immune evasion. [Proc Natl Acad Sci USA] Abstract | Press Release

A Therapeutic Antibody for Cancer, Derived from Single Human B Cells
The authors previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. In an effort to translate these findings into a biologic therapy for cancer, they isolated and expressed DNA sequences encoding high-affinity human CFH antibodies directly from single, sorted B cells obtained from patients with the antibody. [Cell Rep] Full Article | Graphical Abstract | Press Release

HCMV vCXCL1 Binds Several Chemokine Receptors and Preferentially Attracts Neutrophils over NK Cells by Interacting with CXCR2
Researchers showed a unique viral protein, vCXCL1, which targets three chemokine receptors: CXCR1 and CXCR2 expressed on neutrophils and CXCR1 and CX3CR1 expressed on NK cells. Although vCXCL1 attracted both cell types, neutrophils migrated faster and more efficiently than NK cells through the binding of CXCR2. [Cell Rep] Full Article | Graphical Abstract

Exposure to Melan-A/MART-126-35 Tumor Epitope Specific CD8+ T Cells Reveals Immune Escape by Affecting the Ubiquitin-Proteasome System (UPS)
Investigators showed that short-term co-culture of Melan-A/MART-1 tumor antigen-expressing melanoma cells with Melan-A/MART-126-35-specific cytotoxic T lymphocytes (CTL) led to resistance against CTL-induced lysis because of impaired Melan-A/MART-126-35 epitope processing. [Sci Rep] Full Article

Activation-Dependent Cell Death of Human Monocytes Is a Novel Mechanism of Fine-Tuning Inflammation and Autoimmunity
Given the fundamental role of monocyte activation in remodeling the early phases of inflammatory responses, researchers analyzed the GM-CSF/IFN-γ-induced activity of human monocytes in such a situation in vitro and in vivo. [Eur J Immunol] Abstract

Dimethyl Fumarate Activates the Prostaglandin EP2 Receptor and Stimulates cAMP Signaling in Human Peripheral Blood Mononuclear Cells
To determine if dimethyl fumarate (DMF) is able to activate signaling cascades that affect immune dysregulation, scientists treated human peripheral blood mononuclear cells with DMF. They discovered that DMF stimulates cyclic adenosine monophosphate production after one minute treatment in vitro. [Biochem Biophys Res Commun] Abstract

T Cell Bim Levels Reflect Responses to Anti–PD-1 Cancer Therapy
Scientists report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. [JCI Insight]
Full Article | Press Release

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Safety Profiles of Anti-CTLA-4 and Anti-PD-1 Antibodies Alone and in Combination
The authors describe the adverse event profile of checkpoint inhibitors targeting CTLA-4 and PD-1, used both as monotherapies and in combination and aim to provide some general guidelines, based upon the mechanisms of action of these therapies and on the management of these immune-related adverse events. [Nat Rev Clin Oncol] Abstract

Epigenetic Regulation of Adaptive NK Cell Diversification
Focusing on responses to viruses, the authors review similarities and differences between mouse and human adaptive natural killer (NK) cells, identifying molecular analogies that may be key to transcriptional reprogramming and functional alterations. [Trends Immunol] Abstract

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PureTech Teams with Siddhartha Mukherjee to Launch Vor BioPharma to Advance Novel Targeting Platform to Expand Applicability of CAR T-Cell Immunotherapies in Immuno-Oncology
PureTech Health plc announced the launch of Vor BioPharma, an immuno-oncology company dedicated to developing a new class of targeted cell therapies. The company, which is advancing a novel approach to chimeric antigen receptor (CAR) T-cell therapy, has licensed its core technology from the lab of Vor scientific co-founder, Siddhartha Mukherjee, M.D., Ph.D. [PureTech Health plc (Business Wire)] Press Release

Immune Design and Gritstone Oncology Announce Clinical Collaboration for Neoantigen Cancer Immunotherapy
Immune Design and Gritstone Oncology announced a clinical collaboration for development of novel, personalized immunotherapies combining both companies’ leading technologies. The collaboration will involve the application of Immune Design’s ZVex™ discovery platform with Gritstone’s proprietary genomics and proteomics platform for identification of patient-specific tumor antigens to develop neoantigen-based immunotherapies. [Immune Design] Press Release

OncBioMune Submits Protocol to Principal Investigators for Two Phase II Clinical Trials of ProscaVax for Prostate Cancer
OncBioMune Pharmaceuticals, Inc. announced that the protocol has been submitted to the principal investigator for the planned Phase II clinical trial to be hosted by a major university in the Northeast United States and its network of cancer centers. [OncBioMune Pharmaceuticals, Inc. (Marketwired L.P.)] Press Release

NewLink Genetics Announces Results from Phase III IMPRESS Trial of Algenpantucel-L for Patients with Resected Pancreatic Cancer
NewLink Genetics Corporation announced results of its Phase III clinical trial for algenpantucel-L for patients with resected pancreatic cancer. The IMPRESS Phase III study of algenpantucel-L for patients with resected pancreatic cancer did not achieve its primary endpoint. [NewLink Genetics Corporation] Press Release

First Dosing of Pfizer DART Candidate in Phase I Study Triggers Milestone Payment to MacroGenics
MacroGenics, Inc. announced that its collaboration partner, Pfizer Inc. has advanced a bispecific antibody therapeutic candidate generated by MacroGenics’ Dual-Affinity Re-Targeting, or DART®, platform. [MacroGenics, Inc.] Press Release

VAXIMM Initiates Phase IIa Study in Advanced Colorectal Cancer with Oral T-Cell Vaccine VXM01
VAXIMM AG announced the enrollment of the first patient in a Phase IIa clinical trial. The study will enroll 24 patients with metastatic colorectal cancer whose disease has progressed following one or two prior therapies. [VAXIMM AG] Press Release

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NEW Pediatric Infectious Diseases 2016
June 20-23, 2016
Hilton Head Island, United States

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NEW Postdoctoral Fellowship – Immunology (Tongji Medical College)

Research Technologist – T Cell Immunology (STEMCELL Technologies Inc.)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Scientist – Bioengineering (STEMCELL Technologies Inc.)

Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Immunology (Technische Universität München)

Postdoctoral Fellow – Cancer Biology & Cancer Immunology (Fox Chase Cancer Center)

Postdoctoral Position – Immunology (Erasmus MC)

Faculty Positions – Microbiology and Immunology (National University of Singapore)

Postdoctoral Fellow – Immunology (University of Wisconsin – Madison)

Postdoctoral Researchers – Tumor Immunology and Cancer Immunotherapy (University of California, Los Angeles)

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