Human Immunology News Volume 5.14 | Apr 11 2017

TOP STORY

Dectin 1 Activation on Macrophages by Galectin 9 Promotes Pancreatic Carcinoma and Peritumoral Immune Tolerance

Scientists found that dectin 1 can ligate the lectin galectin 9 in mouse and human pancreatic ductal adenocarcinoma (PDA), which results in tolerogenic macrophage programming and adaptive immune suppression. Upon disruption of the dectin 1–galectin 9 axis, CD4⁺ and CD8⁺ T cells, which are dispensable for PDA progression in hosts with an intact signaling axis, become reprogrammed into indispensable mediators of anti-tumor immunity. [Nat Med] Abstract | Press Release

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Thymosin α1 Represents a Potential Potent Single-Molecule-Based Therapy for Cystic Fibrosis

The authors report on the ability of thymosin alpha 1—a naturally occurring polypeptide with an excellent safety profile in the clinic when used as an adjuvant or an immunotherapeutic agent—to rectify the multiple tissue defects in mice with cystic fibrosis as well as in cells from subjects with the p.Phe508del mutation. [Nat Med] Abstract | Press Release

Progenitor T-Cell Differentiation from Hematopoietic Stem Cells Using Delta-Like-4 and VCAM-1

Investigators describe a fully defined engineered in vitro niche capable of guiding T-lineage development from hematopoietic stem and progenitor cells. Synergistic interactions between Notch ligand Delta-like 4 and vascular cell adhesion molecule 1 (VCAM-1) were leveraged to enhance Notch signaling and progenitor T-cell differentiation rates. [Nat Methods] Abstract

Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cell-Mediated Colon Cancer Progression

Scientists found that high hematopoietic cell kinase (HCK) levels correlated with reduced survival of colorectal cancer patients. Likewise, increased Hck activity in mice promoted the growth of endogenous colonic malignancies and of human colorectal cancer cell xenografts. Furthermore, tumor-associated macrophages of the corresponding tumors showed a pronounced alternatively activated endotype, which occured independently of mature lymphocytes or of Stat6-dependent Th2 cytokine signaling. [Cancer Cell] Abstract | Graphical Abstract

Foxp3 Exhibits Antiepileptic Effects in Ictogenesis Involved in TLR4 Signaling

Researchers investigated the role of forkhead transcription factor 3 (Foxp3), a transcription factor that is involved in T-cell differentiation, in epileptogenesis. In both human epileptic tissues and experimental seizure models, they found significant up-regulation of Foxp3 in neurons and glial cells. [FASEB J] Abstract

CRISPR/Cas9-Mediated PD-1 Disruption Enhances Anti-Tumor Efficacy of Human Chimeric Antigen Receptor T Cells

The authors showed that programmed death ligand 1 (PD-L1) expression on tumor cells can render human chimeric antigen receptor (CAR) T cells (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired tumor clearance in a sub-cutaneous xenograft model. To overcome this suppressed anti-tumor response, they developed a protocol for combined Cas9 ribonucleoprotein-mediated gene editing and lentiviral transduction to generate programmed cell death protein 1 (PD-1) deficient anti-CD19 CAR T cells. [Sci Rep] Full Article

CXCL17 Attenuates Imiquimod-Induced Psoriasis-Like Skin Inflammation by Recruiting Myeloid-Derived Suppressor Cells and Regulatory T Cells

Researchers examined the role of CXCL17 in skin disorders. CXCL17 mRNA levels in psoriasis skin, but not in lesional skin of atopic dermatitis or cutaneous T cell lymphoma, were significantly higher than those in normal skin. CXCL17 was mainly expressed in the epidermis, and IFN-γ dose-dependently increased CXCL17 expression by human keratinocytes in vitro. [J Immunol] Abstract

Dominant TNFα and Impaired IL-2 Cytokine Profiles of CD4⁺ T Cells from Children with Type-1-Diabetes

Investigators compared memory CD4⁺ T-cell activation and cytokine expression as well as sensitivity to interleukin-7 in vitro between patients with type-1-diabetes at clinical onset, long-term symptomatic disease, and matched healthy controls. They concluded that long-term symptomatic type-1-diabetes patients differed in memory T-cell cytokine profiles and interleukin-7 co-stimulation. [Immunol Cell Biol] Abstract

Transforming Growth Factor β Is a Poor Prognostic Factor and Inhibits the Favorable Prognostic Value of CD8⁺ CTL in Human Hepatocellular Carcinoma

Scientists investigated the prognostic value of measuring transforming growth factor β (TGF-β) and CD8⁺ cytotoxic T lymphocyte (CTL) levels and their relationship in human hepatocellular carcinoma (HCC). Immunohistochemical staining was conducted to analyze the prognostic value of TGF-β expression and/or CD8⁺ CTLs levels in 407 HCC patients. [J Immunother] Abstract

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Altered B Cell Signaling in Autoimmunity

The authors summarize how, rather than being a downstream consequence of autoreactive T cell activation, dysregulated B cell signaling can function as a primary driver of many human autoimmune diseases. [Nat Rev Immunol] Abstract

Molecular Checkpoints Controlling Natural Killer Cell Activation and their Modulation for Cancer Immunotherapy

Scientists discuss how natural killer (NK) cells have gained considerable attention as promising therapeutic tools for cancer therapy due to their innate selectivity against cancer cells over normal healthy cells. The redundancy of synergizing receptors and the inhibition of NK cell function by a single class of inhibitory receptor suggest the presence of common checkpoints to control NK cell activation through different receptors. These molecular checkpoints would be therapeutically targeted to harness the power of NK cells against diverse cancer cells that express heterogeneous ligands for NK cell receptors. [Exp Mol Med] Full Article

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Developing Adoptive T-Cell Therapy for Ovarian Cancer

Dr. Kristin Anderson from Fred Hutch described preclinical research on T-cell therapy showing how engineered T cells are able to kill both human and mouse ovarian cancer cells in the lab and significantly extend survival in a mouse model. [Press release from the Fred Hutchinson Cancer Research Center discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release

Agenus Commences Phase I Trial with Neoantigen Cancer Vaccine AutoSynVax™

Agenus Inc. announced that the first patient has been dosed in a Phase I clinical trial of AutoSynVax™ (ASV™), Agenus’ neoantigen vaccine. [Press release from Agenus Inc. discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release

Nanoparticle Treatment Could Improve Immunotherapy against Cancer

Researchers at the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center have discovered a potential novel strategy for improving drugs that unleash the immune system against cancer — by binding two compounds to a nanoparticle. [Press release from UNC Lineberger discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release

Promising New Cancer Therapy Developed via Michigan State University and Venn Therapeutics Partnership

Michigan State University researchers presented promising cancer therapy results. The novel technology, AdVCA0848, activates the stimulator of interferon genes pathway to delay tumor growth in a B16 melanoma model, promoting beneficial anti-tumor responses. [Press release from the Michigan State University discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release

UNC Lineberger Receives $4 Million Gift to Support Promising New Cancer Treatment

Alice Lehman of Charlotte has donated $4 million to the University of North Carolina at Chapel Hill to help fund the new cellular immunotherapy research program at UNC Lineberger Comprehensive Cancer Center. [UNC Lineberger] Press Release

The Human Vaccines Project, Vanderbilt and Illumina Join Forces to Decode the Human Immunome

The Human Vaccines Project and Vanderbilt University Medical Center announced that they joined forces with Illumina, Inc., to decipher the human immunome, the genetic underpinnings of the immune system. Illumina will provide the genetic sequencing technologies and expertise required to process the massive amounts of data required to decode the human immunome. [Vanderbilt University Medical Center] Press Release

LLS Expands Innovative Therapy Acceleration Program with Novel Immunotherapy

The Leukemia & Lymphoma Society (LLS) continues to advance the promising field of immunotherapy research, harnessing the body’s own immune system to fight cancer, with a $4 million funding commitment in an investigational therapy being developed by Forty Seven Inc. for lymphoma patients. [The Leukemia & Lymphoma Society] Press Release

Review of Canadian Science Calls for Better Oversight, Coordination — and More Money

To reinvigorate its science base, Canada needs to “reinvest” almost CAD $500 million in basic, investigator-led research over the next four years, according to a long-awaited review of the country’s science and innovation landscape. [ScienceInsider] Editorial

Critics Worry Faster FDA Drug Reviews Could Compromise Safety

For biotechs, waiting for new drugs to be approved is not as hard as it used to be. Since late last year, federal regulators have acted months earlier than expected to OK a bumper crop of new drugs from Massachusetts companies. The speedy decisions are welcomed by businesses that have made massive investments in developing experimental medicines and are eager for them to start generating revenue. But critics say the Food and Drug Administration (FDA)’s hurry-up mode may sacrifice patient safety — accelerating under pressure not only from the industry and investors, but from a regulation-averse Trump administration. [Boston Globe Media Partners, LLC] Editorial

U.S. Report Calls for Research Integrity Board

The U.S. research community needs to do a better job of both investigating misconduct allegations and promoting ethical conduct—or the government might act unilaterally in ways that scientists won’t like. That’s the implicit message sent by a new report out from the National Academies of Science, Engineering, and Medicine entitled Fostering Integrity in Research. [ScienceInsider] Editorial

NEW GRKs and Arrestins: From Structure to Disease
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NEW Postdoctoral Scholar – Multiple Sclerosis (University of Washington)

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