Immune Regulation News Volume 11.00 | Jan 11 2019

TOP STORY

Mitochondria Linked to Autoimmunity

Scientists have demonstrated that a specific mitochondrial protein complex is essential to the immunosuppressive activity of regulatory T-cells, findings with potential significance for a wide variety of autoimmune diseases. [Press release from Northwestern University discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Tissue-Resident Memory CD8⁺ T Cells Promote Melanoma-Immune Equilibrium in Skin

Using a mouse model of transplantable cutaneous melanoma, investigators showed that tissue-resident memory CD8⁺ T cells promote a durable melanoma-immune equilibrium that is confined to the epidermal layer of the skin. [Nature] Abstract

Commensal-Specific T Cell Plasticity Promotes Rapid Tissue Adaptation to Injury

Scientists explored whether commensal-specific T cells can act as tissue sentinels, allowing rapid adaptation to defined injuries, and how dysregulation of these responses may have pathogenic consequences. [Science] Full Article

Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10

Investigators found that some plasma cells in the CNS of mice with experimental autoimmune encephalomyelitis originate in the gut and produce immunoglobulin A (IgA). [Cell] Abstract | Press Release 1 | Press Release 2 | Graphical Abstract

Efferocytosis Fuels Requirements of Fatty Acid Oxidation and the Electron Transport Chain to Polarize Macrophages for Tissue Repair

Researchers report the metabolome of activated macrophages during efferocytosis to reveal an IL-10 cytokine escalation that was independent of glycolysis yet bolstered by apoptotic cell fatty acids and mitochondrial β-oxidation, the electron transport chain, and heightened coenzyme NAD⁺. [Cell Metab] Abstract | Graphical Abstract

Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1-CD8⁺ Tumor-Infiltrating T Cells

The authors examined the dynamics of the effector response of CD8⁺ tumor-infiltrating lymphocytes (TILs) after checkpoint blockade therapy. Bulk and single-cell RNA profiles of CD8⁺ TILs after combined Tim-3+PD-1 blockade in preclinical models revealed significant changes in the transcriptional profile of PD-1⁻TILs. [Immunity] Abstract | Graphical Abstract

Intratumoral Tcf1⁺PD-1⁺CD8⁺ T Cells with Stem-Like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy

Scientists identified a subset of tumor-reactive tumor-infiltrating CD8⁺ T lymphocytes bearing hallmarks of exhausted cells and central memory cells, including expression of the checkpoint protein PD-1 and the transcription factor Tcf1. [Immunity] Abstract | Graphical Abstract

Impaired Immune Surveillance Accelerates Accumulation of Senescent Cells and Aging

Investigators showed that Prf1^−/− mice with impaired cell cytotoxicity exhibit both higher senescent-cell tissue burden and chronic inflammation. They suffer from multiple age-related disorders and lower survival. Strikingly, pharmacological elimination of senescent-cells by ABT-737 partially alleviates accelerated aging phenotype in these mice. [Nat Commun] Full Article | Press Release

CD73 Expression on Effector T Cells Sustained by TGF-β Facilitates Tumor Resistance to Anti-4-1BB/CD137 Therapy

Researchers demonstrated an inhibitory role of ecto-enzyme CD73 for agonistic anti-4-1BB/CD137 antibody (Ab) therapy. In particular, anti-4-1BB treatment preferentially drove CD73⁻ effector T cell response for tumor inhibition. Anti-CD73 neutralizing Ab further improved anti-4-1BB therapy associated with enhanced anti-tumor T cell immunity. [Nat Commun] Full Article

IL-15 Is a Component of the Inflammatory Milieu in the Tumor Microenvironment Promoting Antitumor Responses

Scientists report, in analyses of mice implanted with various tumor cell lines, soluble IL-15/IL-15Rα complexes were abundant in the interstitial fluid of tumors with expression preceding the infiltration of tumor-infiltrating lymphocytes. [Proc Natl Acad Sci USA] Abstract

A Role for BATF3 in T_H9 Differentiation and T-Cell-Driven Mucosal Pathologies

Investigators identified TL1A, a member of the TNF superfamily, as a strong inducer of mouse and human T helper 9 (T_H9) differentiation. Mechanistically, TL1A induced the expression of the transcription factors BATF and BATF3 and facilitated their binding to the Il9 promoter leading to enhanced secretion of IL-9. [Mucosal Immunol] Abstract

Blockade of CTLA-4 and Tim-3 Pathways Induces Fetal Loss with Altered Cytokine Profiles by Decidual CD4⁺T Cells

Researchers showed that in animal studies, treatment with either CTLA-4- or Tim-3-blocking antibody caused greater susceptibility to fetal loss with altered cytokine profiles by decidual CD4⁺T (dCD4⁺T) cells. CTLA-4 and Tim-3 pathways appeared to play key roles in maintaining maternal-fetal tolerance by regulating the function of dCD4⁺T cells. [Cell Death Dis] Full Article

Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling and Increases Survival in Cancer Cachexia Syndrome

The authors showed that both genetic ablation and pharmacological inhibition of TLR4 were able to attenuate the main clinical markers of cachexia in mice bearing Lewis lung carcinoma (LLC). Adipose tissue remodeling was not found in LLC tumor-bearing TLR4^−/− mice due to reduced macrophage infiltration and adipocyte atrophy. [Sci Rep] Full Article

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Developing Role of B Cells in the Pathogenesis and Treatment of Chronic GvHD

Scientists introduce the newest studies and examine the role of B cells in chronic graft‐versus‐host disease (GvHD) in detail with respect to the following aspects: altered B cell subpopulations, aberrant B cell signalling pathways, autoantibodies and T‐B cell interactions. [Br J Haematol] Full Article

Cutaneous Immune Responses Mediated by Dendritic Cells and Mast Cells

The authors discuss the known functions of cutaneous DC populations and mast cells and recent studies highlighting their roles within cellular networks that determine cutaneous immune responses. [JCI Insight] Full Article

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Corvus Announces Presentation of Preclinical Data on CPI-818, a First-in-Class Covalent Inhibitor of ITK Targeting T-Cell Lymphomas

Corvus Pharmaceuticals, Inc. announced data from a preclinical study of CPI-818, its investigational small molecule T-cell signaling pathway inhibitor. [Press release from Corvus Pharmaceuticals, Inc. discussing research presented at the 11^th Annual T-Cell Lymphoma Forum, La Jolla] Press Release

Corbus Pharma Enters Strategic Collaboration with Kaken Pharmaceutical Co., Ltd. to Develop and Commercialize Lenabasum in Japan for Systemic Sclerosis and Dermatomyositis

Corbus Pharmaceuticals Holdings, Inc. announced that they have entered into a strategic collaboration with Kaken Pharmaceutical Co., Ltd. for the development and commercialization in Japan of Corbus’ investigational drug lenabasum for the treatment of systemic sclerosis and dermatomyositis, two rare and serious autoimmune diseases. [Corbus Pharmaceuticals Holdings, Inc.] Press Release

NantKwest Announces Launch of Merkel Cell Carcinoma Phase II Trial Deploying Novel Triple Combination of Off-the-Shelf Natural Killer haNK^Ⓡ Cell Therapy with Superagonist IL-15 Cytokine Therapy and PD-l1 Checkpoint Inhibitor Therapy

NantKwest Inc. announced the launch of a novel triple combination, Phase II clinical trial in Merkel cell carcinoma. [NantKwest Inc.] Press Release

Pfizer Initiates Phase IIb/III Clinical Trial for PF-06651600, an Oral JAK3 Inhibitor, for the Treatment of Patients with Moderate to Severe Alopecia Areata

Pfizer Inc. announced the initiation of a Phase IIb/III clinical trial for its oral JAK3 inhibitor, PF-06651600, for the treatment of patients with moderate to severe alopecia areata, a chronic autoimmune skin disease that causes hair loss on the scalp, face, or body, and currently has no approved therapies. [Pfizer Inc.] Press Release

Viela Bio Announces Inebilizumab Achieved Primary and Key Secondary Endpoints in Pivotal Trial in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD)

Viela Bio announced that N-MOmentum, a pivotal trial of inebilizumab, met its primary and key secondary endpoints in patients with NMOSD. The N-MOmentum trial is a randomized, double-masked, placebo-controlled, global registration study that enrolled 231 patients with NMOSD—a rare, life-threatening autoimmune disease affecting the central nervous system. [Viela Bio] Press Release

Crowdfunding Research Flips Science’s Traditional Reward Model

No papers? No problem. Scientists who have historically been at a disadvantage when pursuing traditional funding sources — for example, those who lack extensive experience or who do not demonstrate a good publication record — are now the most successful at sourcing money from the public. [Nature News] Editorial

Serbia Is Rethinking Science — But the Reforms Could Cost Hundreds of Jobs

Serbia is making sweeping reforms to its ailing science system as part of its efforts to join the European Union — but some scientists say the changes could do more harm than good. [Nature News] Editorial

NEW Keystone Symposia: Cancer Immunotherapy: Mechanistic Insights to Improve Clinical Benefit
March 10-14, 2019
Whistler, British Columbia, Canada

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NEW Postdoctoral Fellow – Immunology (Yonsei Cancer Center)

NEW Postdoctoral Fellowship – Cancer Immunology and Immunotherapy (Columbia Center for Translational Immunology)

NEW PhD Position – Epigenetics of Melanoma Immunotherapy Response (University of Otago)

Research Technologist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Scientist – Molecular Innate Immunity (Cedars-Sinai Medical Center)

Supervisor – Transfusion Medicine – Immune, Progenitor, & Cell Therapy (Mayo Clinic-Rochester)

Assistant/Associate or Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

Postdoctoral Fellow/Research Associate – Immunology (Turnstone Biologics Inc.)

Postdoctoral Position – Immunology (Ludwig-Maximilians-Universität)

Postdoctoral Position – Natural Killer Cells (The Scripps Research Institute)

Faculty Positions – Translational Immunology (University of Miami)

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