Human Immunology News 4.49 December 13, 2016 | |
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TOP STORYT-Cell Transfer Therapy Targeting Mutant KRAS in Cancer Researchers identified a polyclonal CD8+ T-cell response against mutant KRAS G12D in tumor-infiltrating lymphocytes obtained from a patient with metastatic colorectal cancer. They observed objective regression of all seven lung metastases after the infusion of approximately 1.11×1011 HLA-C*08:02–restricted tumor-infiltrating lymphocytes that were composed of four different T-cell clonotypes that specifically targeted KRAS G12D. [N Engl J Med] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)Neutrophils Induce Proangiogenic T Cells with a Regulatory Phenotype in Pregnancy Scientists report that human neutrophils exposed to pregnancy hormones progesterone and estriol promote the establishment of maternal tolerance through the induction of a population of CD4+ T cells displaying a GARP+CD127loFOXP3+ phenotype following antigen activation. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release Islet-Derived CD4 T-Cells Targeting Proinsulin in Human Autoimmune Diabetes Researchers showed that proinsulin peptides are targeted by islet-infiltrating T-cells from type 1 diabetes patients. They identified hundreds of T-cells from inflamed pancreatic islets of three young type 1 diabetes organ donors with a short disease duration with high risk HLA genes using a direct T-cell receptor sequencing approach without long-term cell culture. [Diabetes] Abstract Investigators showed that activated B cell-like diffuse large B-cell lymphoma cell-lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express a small isoform of FOXP1 and that the 5-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukemia virus- and transposon-mediated insertional mutagenesis screens. [Haematologica] Abstract G-Rich DNA-Induced Stress Response Blocks Type-I-IFN but not CXCL10 Secretion in Monocytes Investigators described a novel type of post-transcriptional regulation of the type-I-IFN response that was induced in monocytes by cytosolic transfection of a short immunomodulatory DNA, a G-tetrad forming CpG-free derivative of the TLR9 agonist ODN2216. [Sci Rep] Full Article Researchers revealed that IL-17A promoted programmed death ligand 1 (PDL1) expression in human and mouse cells. In the murine cancer model, targeting of IL-17A inhibited PDL1 expression in the tumor microenvironment, decreased the percentage of Treg cells in tumor-infiltrating lymphocytes, and promoted CD4+ and CD8+ T cells to secrete interferon gamma. [Oncotarget] Full Article The Immunomodulatory Effects of TNF-α Inhibitors on Human Th17 Cells via RORγt Histone Acetylation Th17-polarized cells from patients with rheumatoid arthritis (RA) produced more interleukin (IL)-17A, IL-17F and IL-22 than those from healthy subjects. Etanercept and adalimumab suppressed IL-17A, IL-17F and IL-22 levels in Th17-polarized cells from healthy subjects and patients with RA. [Oncotarget] Full Article The authors optimized flow cytometry–based fluorescence in situ hybridization for IFN-γ to multicolor flow cytometry that allows for single-cell measurement of mRNA and protein levels. This high-throughput analysis detected Ag-specific human T cells of low frequency. [J Immunol] Abstract A Novel Class of Somatic Mutations in Blood Detected Preferentially in CD8+ Cells Scientists analyzed somatic mutations in blood in 16 patients with relapsing multiple sclerosis and 4 with other neurological autoimmune disease. To facilitate the detection of somatic mutations CD4+, CD8+, CD19+ and CD4−/CD8−/CD19− cell subpopulations were separated. [Clin Immunol] Full Article Indoleamine 2,3-Dioxygenase Regulates T Cell Activity through Vav1/Rac Pathway The authors determined whether indoleamine 2,3-dioxygenase (IDO) induces T-cell immunosuppression through Vav1/Rac signaling pathway, which is a guanine exchange factor-dependent pathway. The correlation between Vav1 mRNA expressions in T cells of tumor infiltrating lymphocytes and the levels of IDO expression in lung cancer tissues from lung cancer patients was detected. [Mol Immunol] Abstract By comparing the effects of selective drugs on the dynamics of CD25 expression during the mitogen stimulation of human peripheral blood lymphocytes, investigators identified distinct Src- and JAK-dependent stages of IL-2R α-chain upregulation. [PLoS One] Full Article Researchers reported that T cells with anti-CD38-chimeric antigen receptors (CAR) eliminated B-cell lymphoma cells expressing CD38. To employ anti-CD38-CAR against acute myeloid leukemia blasts not expressing CD38, it was necessary to induce or increase the intensity of CD38 expression. [Clin Transl Immunology] Full Article Subscribe to our sister publications: Immunology of Infectious Disease News & Immune Regulation News. | |
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REVIEWSTissue-Resident Natural Killer Cells in the Livers The authors summarize the phenotypic and functional features of liver tissue-resident natural killer (trNK) cells, and review current knowledge regarding developmental pathway of liver trNK cells. They also overview recent advances in human liver trNK cells and discuss the striking shared hallmarks of trNK cells in different tissues. [Sci China Life Sci] Abstract Visit our reviews page to see a complete list of reviews in the human immunology research field. | |
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SCIENCE NEWSNantKwest Inc. announced that the company presented results from a preclinical study on the company’s haNK cell therapy program. [Press release from NantKwest Inc. (Business Wire, Inc.) discussing research presented at the San Antonio Breast Cancer Symposium (SABCS), San Antonio] Press Release | |
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INDUSTRY NEWSThermo Fisher Scientific Launches Center of Excellence in Immunotherapy Program Thermo Fisher Scientific announced its Center of Excellence in Immunotherapy Program designed to build strategic collaborations and accelerate research and clinical trials in immuno-oncology around the globe. [Thermo Fisher Scientific Inc.] Press Release Kite Pharma, Inc. and Vitruvian Networks, Inc. announced a strategic partnership to create a software solution to support commercial availability of T-cell therapies. [Kite Pharma, Inc.] Press Release The John Theurer Cancer Center at Hackensack University Medical Center is partnering with the Parker Institute for Cancer Immunotherapy and the Cancer Research Institute as they launch a major collaboration focused on neoantigens, unique cancer markers that researchers believe may hold the key to developing targeted cancer immunotherapies. [The John Theurer Cancer Center at Hackensack University Medical Center (PR Newswire Association LLC.)] Press Release | |
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POLICY NEWSUnder 21st Century Cures Legislation, Stem Cell Advocates Expect Regulatory Shortcuts As the 21st Century Cures Act cleared the U.S. Senate last week, many attendees of the annual World Stem Cell Summit took a victory lap. The meeting assembled some of the lawyers, analysts, and activists who have long pushed for reform of how the U.S. Food and Drug Administration handles regenerative medicine. And the behemoth biomedical bill predicted to get a presidential signature this week could allow some stem cell products a faster and more flexible premarket approval process. [ScienceInsider] Editorial Brexit by the Numbers: The Fear of Brain Drain British universities fear losing large swathes of their research staff as the country faces up to Brexit, the split with the European Union. More than 31,000 academics at UK universities are non-British EU citizens, and so may lose their rights to live in the United Kingdom after Brexit. [Nature Trend Watch] Editorial Italian Scientists Won’t Miss Departing Prime Minister Matteo Renzi Italian politics is in turmoil after the resignation of Prime Minister Matteo Renzi — but researchers say that they are not particularly sad to see him go. In his almost three years in charge, Renzi promised improvements for universities and science but failed to raise the status of research in the country, according to scientists who complain that he also directly interfered in academic affairs. [Nature News] Editorial
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JOB OPPORTUNITIESNEW PhD Student – Cancer Research (University of Otago) NEW Postdoctoral Research Fellow – Melanoma (Dana-Farber Cancer Institute) NEW Scientist/Senior Scientist – Immunology (Vor BioPharma) Postdoctoral Research Fellow – Immune Regeneration (Fred Hutchinson Cancer Research Center) Faculty Positions – Cancer Immunology (University of New Mexico) Postdoctoral Position – Immunology of HIV-1 and Cancer (University of Alabama at Birmingham) Postdoctoral Researcher Position – Immunology/Molecular Biology (Duke University) Postdoctoral Position – Development of Immune System (Lund University) Scientist – T Cells in Autoimmune Diabetes (Helmholtz Zentrum Munchen) Assistant Professor – Microbiology and Immunology (University of California, San Francisco) Postdoctoral Fellow – Molecular Immunology (University of California San Diego School of Medicine) Assistant Associate – Cancer Immunology (Fred Hutchinson Cancer Research Center) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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