Immune Regulation News Volume 11.17 | May 17 2019

TOP STORY

Targeting the CBM Complex Causes T_reg Cells to Prime Tumors for Immune Checkpoint Therapy

Scientists showed that, after disruption of the CARMA1-BCL10-MALT1 (CBM) signalosome complex, most tumor-infiltrating T_reg cells produced IFNγ, resulting in stunted tumor growth. [Nature] Abstract

(Ranked by impact factor of the journal)

Immune Induction Strategies in Metastatic Triple-Negative Breast Cancer to Enhance the Sensitivity to PD-1 Blockade: The TONIC Trial

After doxorubicin and cisplatin induction, researchers detected an upregulation of immune-related genes involved in programmed cell death protein 1 (PD-1)-programmed death ligand 1 and T cell cytotoxicity pathways. [Nat Med] Abstract

BCL2 Amplicon Loss and Transcriptional Remodeling Drives ABT-199 Resistance in B Cell Lymphoma Models

The authors report that resistance to the BCL-2 targeting drug ABT-199 in models of mantle cell lymphoma and double-hit lymphoma evolves from outgrowth of persister clones displaying loss of 18q21 amplicons that harbor BCL2. [Cancer Cell] Abstract | Press Release | Graphical Abstract

Intratumoral Activity of the CXCR3 Chemokine System Is Required for the Efficacy of Anti-PD-1 Therapy

Investigators found that tumor-bearing mice deficient in the chemokine receptor CXCR3 responded poorly to anti-programmed cell death-1 (PD-1) treatment. CXCR3 and its ligand CXCL9 were critical for a productive CD8⁺ T cell response in tumor-bearing mice treated with anti-PD-1 but were not required for the infiltration of CD8⁺ T cells into tumors. [Immunity] Abstract | Graphical Abstract

A20 Prevents Inflammasome-Dependent Arthritis by Inhibiting Macrophage Necroptosis through Its ZnF7 Ubiquitin-Binding Domain

Scientists showed that A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis and that this function depends on its zinc finger 7 (ZnF7). [Nat Cell Biol] Abstract

Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope

Researchers engineered glycans onto influenza virus hemagglutinin and characterized the molecular features of the elicited humoral immunity in mice. They found that glycan addition changed the initially diverse antibody repertoire into an epitope-focused, genetically restricted response. [Cell Host Microbe] Abstract | Graphical Abstract

Skin Immunization Activates an Innate Lymphoid Cell-Monocyte Axis Regulating CD8⁺ Effector Recruitment to Mucosal Tissues

Investigators showed that adenovirus serotype 5 bio-distributes at very low level to non-lymphoid tissues after skin immunization. This drove the expansion and activation of CD3⁻ NK1.1⁺ group 1 innate lymphoid cells within the female reproductive tract, essential for recruitment of CD8⁺ T-cell effectors. [Nat Commun] Full Article

miR-155 Harnesses Phf19 to Potentiate Cancer Immunotherapy through Epigenetic Reprogramming of CD8⁺ T Cell Fate

Scientists showed that miR-155 increased CD8⁺ T cell antitumor function by restraining T cell senescence and functional exhaustion through epigenetic silencing of drivers of terminal differentiation. [Nat Commun] Full Article

CD8⁺ T Cells Promote Maturation of Liver‐Resident NK Cells via the CD70‐CD27 axis

The authors discovered that liver‐resident natural killer (LrNK) cells exhibited a relatively immature phenotype and impaired cytotoxic capacity in the absence of CD8⁺ T cells. The provision of CD8⁺ T cells to Cd8^‐/‐ or Rag1^‐/‐ mice led to the restoration of LrNK cell maturation. [Hepatology] Abstract

The Signaling Adaptor BCAP Inhibits NLRP3 and NLRC4 Inflammasome Activation in Macrophages through Interactions with Flightless-1

Independent of its effects on Toll-like receptor priming, B cell adaptor for phosphoinositide 3-kinase (BCAP) inhibited NLRP3- and NLRC4-induced caspase-1 activation, cell death, and IL-1β release from macrophages. Accordingly, caspase-1-dependent clearance of a Yersinia pseudotuberculosis mutant was enhanced in BCAP-deficient mice. [Sci Signal] Full Article

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Adverse Effects of Immune-Checkpoint Inhibitors: Epidemiology, Management and Surveillance

Scientists provide an overview of the various types of immune-related adverse events that have emerged to date. They discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. [Nat Rev Clin Oncol] Abstract

Regulatory Immune Mechanisms beyond Regulatory T Cells

The authors highlight questions surrounding Treg transfers as putative treatments for autoimmunity. They discuss whether lack of antigenic recognition might be key to shifting cells from contributing to an aggressive autoresponse, to being part of a regulatory network. [Trends Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

Iovance Biotherapeutics Announces Updates to Tumor Infiltrating Lymphocyte (TIL) Therapy Clinical Programs

Iovance Biotherapeutics, Inc. announced updates from ongoing clinical trials including new interim data from studies of TIL therapy LN-145 in patients with advanced cervical cancer and with TIL therapy lifileucel in advanced melanoma. [Press release from Iovance Biotherapeutics, Inc. discussing research to be presented at the 55^th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

Roche’s Personalized Medicine Entrectinib Shrank Tumors Harboring NTRK, ROS1 or ALK Gene Fusions in Children and Adolescents

Roche announced positive data from the Phase I/II STARTRK-NG study, evaluating the investigational medicine entrectinib in children and adolescents with recurrent or refractory solid tumors with and without neurotrophic tyrosine receptor kinase (NTRK), ROS1 or anaplastic lymphoma kinase (ALK) gene fusions. [Press release from F. Hoffmann-La Roche Ltd discussing research to be presented at the 55^th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

Genocea Announces Positive Interim Immunogenicity Data from GEN-009 Neoantigen Vaccine Phase I/IIa Clinical Trial

Genocea Biosciences, Inc. announced the first clinical results from its ongoing Phase I/IIa trial for GEN-009, the company’s lead neoantigen vaccine candidate. [Press release from Genocea Biosciences, Inc. discussing research to be presented at the 55^th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

Intensity Therapeutics to Present Data on Safety, Tumor Regression and Immune Activation of INT230-6

Intensity Therapeutics, Inc. announced that a poster highlighting the safety profile, tumor regression activity and immune activation of the company’s lead product candidate, INT230-6, will be presented. [Press release from Intensity Therapeutics, Inc. discussing research to be presented at the 55^th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

CEL-SCI Presents New Data for Its LEAPS Vaccine in the Treatment of Rheumatoid Arthritis

CEL-SCI Corporation announced that Daniel Zimmerman, Ph.D., its Senior Vice President of Research, Cellular Immunology, presented new LEAPS data. [Press release from CEL-SCI Corporation (Business Wire, Inc.) discussing research presented at the American Association of Immunologists 103^rd Annual Meeting (Immunology 2019), San Diego] Press Release

Genocea Announces Research Collaboration with Iovance to Explore Development of Neoantigen-Targeted TIL (Tumor-Infiltrating Lymphocyte) Products

Genocea Biosciences, Inc. announced a research collaboration with Iovance Biotherapeutics, Inc. to assess the potential of applying Genocea’s neoantigen identification platform, ATLAS™, to next-generation TIL product development. [Genocea Biosciences, Inc.] Press Release

Parvus Therapeutics Enters into Worldwide Collaboration and License Agreement with Genentech to Develop Navacim™ Therapeutics for the Treatment of Autoimmune Diseases

Parvus Therapeutics has entered into a worldwide collaboration and license agreement with Genentech to develop, manufacture, and commercialize novel Navacim™ therapeutics for the treatment of inflammatory bowel disease, autoimmune liver diseases, and celiac disease. [Parvus Therapeutics] Press Release

X4 Pharmaceuticals and The Leukemia & Lymphoma Society Announce Collaboration to Advance Development of Mavorixafor in Waldenström’s Macroglobulinemia

X4 Pharmaceuticals, Inc. and The Leukemia & Lymphoma Society announced a collaboration to accelerate the development of X4’s lead product candidate, mavorixafor for the treatment of Waldenström’s macroglobulinemia, a rare form of non-Hodgkin lymphoma. [X4 Pharmaceuticals, Inc.] Press Release

Tempest Therapeutics Starts Phase I/Ib Clinical Trial with First-in-Class PPAR Alpha Antagonist

Tempest Therapeutics Inc. announced that the first patient has been dosed with TPST-1120 in a Phase I/Ib trial to treat advanced solid tumor malignancies. [Tempest Therapeutics Inc.] Press Release

Cue Biopharma Announces FDA Acceptance of IND for Lead Immuno-Oncology Candidate, CUE-101, in Treatment of HPV-Driven Cancers

Cue Biopharma, Inc. announced the FDA has accepted the company’s Investigational New Drug (IND) application for its lead immuno-oncology candidate, CUE-101, an Immuno-STAT™ biologic, as a potential treatment for HPV-associated cancers. [Cue Biopharma, Inc.] Press Release

PEP-Therapy Reports Positive Results from GLP-Toxicity Study of PEP-010 Drug Candidate

PEP-Therapy announced that its first-in-class drug candidate, PEP-010, successfully completed Good Laboratory Practice (GLP) toxicity study, moving towards its first-in-human clinical trial. [PEP-Therapy] Press Release

Senate Panel Delays Good-Government Bill, Scolds HHS for ‘Moving the Goal Posts’

A Senate panel delayed action on a bipartisan bill to improve government transparency among advisory bodies in deference to concerns from the National Institutes of Health that the legislation would seriously disrupt the agency’s ability to review research proposals. [ScienceInsider] Editorial

To Meet the ‘Plan S’ Open-Access Mandate, Journals Mull Setting Papers Free at Publication

Plan S, the funder-backed scheme to require free online access to scientific literature, aims to shake up the subscription journals that have long dominated scholarly publishing. Now, some publishers are considering an approach they hope will both comply with the plan and maintain their subscription income: allowing authors to post manuscripts in public archives as soon as their papers are published. [ScienceInsider] Editorial

NEW 5^th International Conference Acute Myeloid Leukemia
October 24-26, 2019
Estoril, Portugal

Visit our events page to see a complete list of events in the community.

NEW Researcher – Tumor Responses to Radiotherapy & Immunotherapy (University Hospital of Northern Norway)

Postdoctoral Fellow – Innate Immunity and Inflammation (University of Pennsylvania)

Postdoctoral Fellow – Intracellular Innate Immunity (EPFL)

Postdoctoral Fellow – Transplantation Immunology (Medical College of Wisconsin)

Professorship – Translational Immune Oncology (Uniklinik Köln)

Postdoctoral Position – Immunology of Enteric Infections (University of Utah)

Director of Research – Division of Translational Medicine & Human Genetics (University of Pennsylvania)

Associate Scientist – Immuno-Oncology (HMH Center for Discovery & Innovation)

Postdoctoral Fellow – Cancer Checkpoint Immunotherapy (City of Hope)

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

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