Immune Regulation News 12.01 January 17, 2020 | |
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TOP STORYImmune Landscape of Viral- and Carcinogen-Driven Head and Neck Cancer Immune cells within tumors of human papillomavirus (HPV)–and HPV+ head and neck squamous cell carcinoma displayed a spectrum of transcriptional signatures, with helper CD4+ T cells and B cells being relatively divergent and CD8+ T cells and CD4+ regulatory T cells being relatively similar. Transcriptional results were contextualized through multispectral immunofluorescence analyses and evaluating putative cell-cell communication based on spatial proximity. [Immunity] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Investigators found that intratumoral injection of a tumor-selective oncolytic vaccinia virus encoding IL-7 and IL-12 into tumor-bearing immunocompetent mice activated the inflammatory immune status of previously poorly immunogenic tumors and resulted in complete tumor regression, even in distant tumor deposits. [Sci Transl Med] Full Article The authors describe a stromal cell-autonomous signaling pathway, which contributed to drug resistance of malignant B cells. They showed that protein kinase C-β-dependent signals from bone marrow-derived stromal cells markedly decrease the efficacy of cytotoxic therapies. [Sci Transl Med] Abstract Macropinocytosis Drives T Cell Growth by Sustaining the Activation of mTORC1 Investigators showed that primary mouse and human T cells engage in macropinocytosis that increases in magnitude upon T cell activation to support T cell growth even under amino acid (AA) replete conditions. Mechanistically, macropinocytosis in T cells provided access of extracellular AA to an endolysosomal compartment to sustain activation of the mechanistic target of rapamycin complex 1 (mTORC1) that promotes T cell growth. [Nat Commun] Full Article Arf1 ablation in cancer cells induced mitochondrial defects, endoplasmic-reticulum stress, and the release of damage-associated molecular patterns, which recruited and activated dendritic cells at tumor sites. The activated immune system finally elicited anti-tumor immune surveillance by stimulating T-cell infiltration and activation. [Nat Commun] Full Article High-Dose Ascorbic Acid Synergizes with Anti_PD1 in a Lymphoma Mouse Model Researchers showed that ascorbic acid (AA) treatment caused genomewide demethylation and enhanced expression of endogenous retroviral elements in lymphoma cells. AA also increased 5-hydroxymethylcytosine levels of CD8+ T cells and enhanced their cytotoxic activity in a lymphoma co-culture system. [Proc Natl Acad Sci USA] Full Article Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses Scientists showed that loss of p53 in cancer cells modulated the tumor-immune landscape to circumvent immune destruction. Deletion of p53 promoted the recruitment and instruction of suppressive myeloid CD11b+ cells, in part through increased expression of CXCR3/CCR2-associated chemokines and macrophage colony-stimulating factor, and attenuated the CD4+ T helper 1 and CD8+ T cell responses in vivo. [Cell Rep] Full Article | Graphical Abstract Researchers showed that superantigen-producing Staphylococcus aureus (SAg-Sau) drove a strong Th17 activation, which was associated with an impaired CD4+ T cell-mediated immune regulation. This impairment of immune control correlated with a significant downregulation of IL-35 expression in tonsillar CD4+ T cells by SAg-Sau. [Mucosal Immunol] Full Article Scientists assessed the impact of the MCT1 inhibitor AZD3965 on tumor metabolism and immune cell infiltration as key determinants of tumor biological function in the MCT1-dependent Raji B cell lymphoma model. Treatment of Raji xenograft-bearing severe combined immunodeficiency mice with AZD3965 led to inhibition of tumor growth paralleled with a decrease in tumor choline, as detected by non-invasive in vivo proton nuclear magnetic resonance spectroscopy. [Br J Cancer] Full Article Knockdown of Sodium Channel Nax Reduces Dermatitis Symptoms in Rabbit Skin Nax is a sodium channel that regulated inflammatory gene expression in response to perturbation of barrier function of the skin. Investigators found that in vivo knockdown of Nax using RNAi reduced hyperkeratosis and keratinocyte hyperproliferation in rabbit ear dermatitic skin. Increased infiltration of inflammatory cells, a characteristic of dermatitis, was reduced by Nax knockdown. [Lab Invest] Abstract Immunophenotyping Monocytes, Macrophages and Granulocytes in the Pteropodid Bat Eonycteris spelaea Bat cells often resembled their human counterparts when comparing immune parameters that are divergent between humans and mice, such as the expression patterns of certain immune cell markers. A genome-wide comparison of immune-related genes also revealed a much closer phylogenetic relationship between bats and humans compared to rodents. [Sci Rep] Full Article HDAC10 Deletion Promotes Foxp3+ T-Regulatory Cell Function Scientists investigated the effect of HDAC10 in murine Tregs. HDAC10 deletion had no adverse effect on the health of mice, which retained normal CD4+ and CD8+ T cell function. However, HDAC10−/− Treg exhibited increased suppressive function in vitro and in vivo. [Sci Rep] Full Article Subscribe to our sister publications: Human Immunology News & Immunology of Infectious Disease News. | |
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REVIEWSTop 10 Challenges in Cancer Immunotherapy The authors define ten key challenges facing cancer immunotherapy, which range from lack of confidence in translating pre-clinical findings to identifying optimal combinations of immune-based therapies for any given patient. Addressing these challenges will require the combined efforts of basic researchers and clinicians, and the focusing of resources to accelerate understanding of the complex interactions between cancer and the immune system and the development of improved treatment options for patients with cancer. [Immunity] Abstract Tumor Immunology and Tumor Evolution: Intertwined Histories Investigators discuss the involvement of different immune cells at distinct stages of tumor progression and how immune contexture determinants shaping tumor development are being exploited therapeutically. Current clinical stratification schemes focus on the tumor histopathology and the molecular characteristics of the tumor cell. [Immunity] Abstract Innate Immunity in Diabetic Kidney Disease Increasing evidence suggests that renal inflammation contributes to the pathogenesis and progression of diabetic kidney disease (DKD) and that anti-inflammatory therapies might have renoprotective effects in DKD. Immune cells and resident renal cells that activate innate immunity have critical roles in triggering and sustaining inflammation in this setting. [Nat Rev Nephrol] Abstract Visit our reviews page to see a complete list of reviews in the immune regulation research field. | |
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INDUSTRY NEWSEmerald Health Pharmaceuticals Inc. announced that the FDA has cleared its investigational new drug (IND) application for EHP-101, an oral product candidate of a patented new chemical entity for the treatment of patients with systemic sclerosis (SSc), a severe form of scleroderma. [Emerald Health Pharmaceuticals Inc.] Press Release Iovance Biotherapeutics Obtains License to Develop and Commercialize a Novel IL-2 Analog Iovance Biotherapeutics, Inc. announced that the company has obtained a license from Novartis to develop and commercialize an antibody cytokine engrafted protein, referred to as IOV-3001. [Iovance Biotherapeutics, Inc.] Press Release OSE Immunotherapeutics announced that the Japanese Patent Office has issued a new patent family related to Tedopi®, a combination of neoepitopes, protecting the product’s method for inducing early T-lymphocyte memory response for use in the treatment of cancer in HLA-A2 positive patients. This patent provides a protection until 2035. [OSE Immunotherapeutics] Press Release | |
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POLICY NEWSSenate Bill Would Boost Spending on Trump Administration’s Research Priorities A bipartisan group of senators asked the Trump administration to pump up funding for a handful of technologies they believe will drive future US economic growth. And the top White House technology officer thinks it’s a great idea. [ScienceInsider] Editorial Florida Cracks Down on Foreign Government Involvement in Research Florida is launching a statewide investigation into US research exploitation after four University of Florida faculty members and six employees of Moffitt Cancer Center in Tampa failed to disclose ties to foreign programs, reports the Tampa Bay Times. [The Scientist] Editorial
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