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tumor immunity

Rindert Missiaen, Massimiliano Mazzone, Gabriele Bergers
Tumor angiogenesis and escape of immunosurveillance are two cancer hallmarks that are tightly linked and reciprocally regulated by paracrine signaling cues of cell constituents from both compartments. Formation and remodeling of new blood vessels in tumors is abnormal and facilitates immune evasion. In turn, immune cells in the tumor, specifically in context with an acidic and hypoxic environment, can promote neovascularization. Immunotherapy has emerged as a major therapeutic modality in cancer but is often hampered by the low influx of activated cytotoxic T-cells...
June 20, 2018: Seminars in Cancer Biology
Xin Zhang, Jane E Hartung, Andrey V Bortsov, Seungtae Kim, Sandra C O'Buckley, Julia Kozlowski, Andrea G Nackley
Functional pain syndromes, such as fibromyalgia and temporomandibular disorder, are associated with enhanced catecholamine tone and decreased levels of catechol-O-methyltransferase (COMT; an enzyme that metabolizes catecholamines). Consistent with clinical syndromes, our lab has shown that sustained 14-day delivery of the COMT inhibitor OR486 in rodents results in pain at multiple body sites and pain-related volitional behaviors. The onset of COMT-dependent functional pain is mediated by peripheral β2 - and β3 -adrenergic receptors (β2 - and β3 ARs) through the release of the pro-inflammatory cytokines tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and interleukin-6 (IL-6)...
June 20, 2018: Brain, Behavior, and Immunity
Sergey Nikulshin, Linda Kundzina, Iveta Tolstikova, Dagne Gravele, Tatjana Prokofjeva, Dace Gardovska
Age and gender-related variability of main lymphocyte subsets (T, B and NK cell absolute counts and percentages from Ly; T4, T8 and DN cell absolute counts and percentages from lymphocytes and from T cells; T4:T8 and T:B ratios) was studied in a large cohort of pediatric patients (2 days - 17 years) at yearly intervals. 4128 6-color TBNK tests performed on BD FACSCanto II flow cytometer were assessed; patients with immune deficiencies and tumors were not included. The study revealed significant age and gender-related changes in all subsets...
June 23, 2018: Scandinavian Journal of Immunology
Jennifer K Colby, Jonathan Jaoude, Fuyao Liu, Imad Shureiqi
Polyunsaturated fatty acids (PUFAs) are enzymatically converted to a variety of bioactive products through insertion of molecular oxygen. PUFA-derived mediators can have either inflammatory or anti-inflammatory/pro-resolving properties, depending upon their specific structures. The relative harm or benefit of these mediators can also be tissue and context dependent. These mediators play important roles in maintaining homeostasis and their dysregulation is involved in pathogenesis of cancers, especially those associated with chronic inflammation...
June 22, 2018: Cancer Metastasis Reviews
Pengfei Xue, Xiaojuan Liu, Yiming Shen, Yuanyuan Ju, Xiongsong Lu, Jinlong Zhang, Guanhua Xu, Yuyu Sun, Jiajia Chen, Haiyan Gu, Zhiming Cui, Guofeng Bao
E3 ubiquitin ligase c-Caritas B cell lymphoma (c-cbl) is associated with negative regulation of receptor tyrosine kinases, signal transduction of antigens and cytokine receptors, and immune response. However, the expression and function of c-cbl in the regulation of neuropathic pain after chronic constriction injury (CCI) are unknown. In rat CCI model, c-cbl inhibited the activation of spinal cord microglia and the release of pro-inflammatory factors including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), which alleviated mechanical and heat pain through down-regulating extracellular signal-regulated kinase (ERK) pathway...
June 22, 2018: Neurochemical Research
Andrea C Chaikovsky, Julien Sage
Inhibitors of the cyclin-dependent kinases 4 and 6 (CDK4/6) were originally designed to block proliferation and cell cycle progression of cancer cells in which the activity of these kinases is dysregulated. CDK4/6 inhibitors have already been FDA-approved for the treatment of estrogen receptor (ER)-positive breast cancer and are being tested in numerous other cancer types. However, several recent studies have identified novel effects of CDK4/6 inhibitors on tumor growth, most notably an indirect effect resulting from the activation of immune surveillance...
June 22, 2018: Molecular Cancer Research: MCR
Meixuan Chen, Barbara Pockaj, Mariacarla Andreozzi, Michael T Barrett, Sri Krishna, Seron Eaton, Ruifang Niu, Karen S Anderson
BACKGROUND: Activation of the JAK/STAT pathway is common in triple-negative breast cancer (TNBC) and affects the expression of genes controlling immune signaling. A subset of TNBC cases will have somatic amplification of chromosome 9p24.1, encoding PD-L1, PD-L2, and JAK2, which has been associated with decreased survival. MATERIALS AND METHODS: Eleven TNBC cell lines were evaluated using array comparative genomic hybridization. A copy number gain was defined as an array comparative genomic hybridization log2 ratio of ≥ 1...
May 26, 2018: Clinical Breast Cancer
Zhiwen Wang, Yu Huang, Yuan Li, Bei Wang, Yishan Lu, Liqun Xia, Jufen Tang, JiChang Jian
Nile tilapia (Oreochromis niloticus) is a pivotal economic fish that has been plagued by Streptococcus agalactiae infections for many years. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a crucial adaptor molecule of the interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily, which can trigger downstream signaling cascades involved in innate immunity. In this study, the full-length cDNA of TRAF6 was cloned from O. niloticus (named On-TRAF6), which has an open reading frame of 1716 bp, and encode a polypeptide of 571 amino acids...
June 19, 2018: Fish & Shellfish Immunology
Kenichi Suda, Jihye Kim, Isao Murakami, Leslie Rozeboom, Masaki Shimoji, Shigeki Shimizu, Christopher J Rivard, Tetsuya Mitsudomi, Aik-Choon Tan, Fred R Hirsch
INTRODUCTION: Data regarding the pre-treatment inter-tumor heterogeneity of potential biomarkers in advanced-stage lung cancers is limited. A finding of such heterogeneity between primary and metastatic lesions would prove valuable to determine if a metastatic lesion can be a surrogate for the primary tumor, as more biomarkers will likely be used in the future to inform treatment decisions. METHODS: We performed RNA sequencing to analyze inter-tumor heterogeneity in thirty specimens (primary tumors, intra-thoracic, and extra-thoracic metastatic lesions) obtained from five treatment-naïve lung cancer patients...
June 19, 2018: Journal of Thoracic Oncology
Lara Vecchi, Mariana Alves Pereira Zoia, Tiago Goss Santos, Adriano de Oliveira Beserra, Cristiano Manuel Colaço Ramos, Bruna França Matias Colombo, Yara Cristina Paiva Maia, Victor Piana de Andrade, Sara Teixeira Soares Mota, Thaise Gonçalves de Araújo, Fernanda Van Petten de Vasconcelos Azevedo, Fernando Augusto Soares, Sonia Maria Oliani, Luiz Ricardo Goulart
Breast Cancer (BC) is a highly heterogeneous disease whose most aggressive behavior is displayed by triple-negative breast cancer (TNBC), which lacks an efficient targeted therapy. Despite its controversial role, one of the proteins that having been linked with BC is Annexin A1 (AnxA1), which is a Ca+2 binding protein that acts modulating the immune system, cell membrane organization and vesicular trafficking. In this work we analyzed tissue microarrays of BC samples and observed a higher expression of AnxA1 in TNBCs and in lymph node metastasis...
June 19, 2018: Biochimica et Biophysica Acta
Michael Bartoschek, Kristian Pietras
The development and progression of a tumor depends on the close interaction of malignant cells and the supportive and suppressive tumor microenvironment. Paracrine signaling enables tumor cells to shape the surrounding tissue in order to decrease recognition by the immune system, attract blood vessels to fuel growth, change metabolic programs and induce wound healing programs. In this study, we investigate the role of the platelet-derived growth factor (PDGF) family members PDGFA, PDGFB, PDGFC and PDGFD and their cognate tyrosine kinase receptors PDGFRA and PDGFRB, using publicly available data from The Cancer Genome Atlas and the Human Protein Atlas...
June 19, 2018: Biochemical and Biophysical Research Communications
Tamara Tyrinova, Olga Leplina, Sergey Mishinov, Marina Tikhonova, Anton Kalinovskiy, Sergey Chernov, Evgeniya Dolgova, Vyacheslav Stupak, Evgeniya Voronina, Sergey Bogachev, Ekaterina Shevela, Alexander Ostanin, Elena Chernykh
Besides initiation of tumor-specific T cell immunity, dendritic cells (DCs) are endowed with tumoricidal activity. Previously, we showed that monocyte-derived DCs of high-grade glioma patients generated in the presence of interferon alpha (IFNα) (IFN-DCs) have impaired cytotoxic activity against tumor necrosis factor alpha (TNFα)-sensitive HEp-2 tumor cells. Herein, we demonstrate that decreased transmembrane TNFα (tmTNFα) expression, but not soluble TNFα (sTNFα) production by high-grade glioma patient IFN-DCs, determines the defective tumoricidal activity against TNFα-sensitive HEp-2 cells...
June 22, 2018: Journal of Interferon & Cytokine Research
Pengxiang Yang, Huijuan Song, Yibo Qin, Pingsheng Huang, Chuangnian Zhang, Deling Kong, Weiwei Wang
Dendritic cells (DCs) are increasingly used in cancer vaccines due to their ability to regulate T-cell immunity. Major limitations associated with the present DCs adoptive transfer immunotherapy are low cell viability and transient duration of transplanted DCs at the vaccination site, and the lack of recruitment of host DCs, leading to unsatisfactory T-cell immune response. Here, we developed a novel vaccine nodule comprising a simple physical mixture of the peptide nanofibrous hydrogel, DCs and tumor antigens...
June 22, 2018: Nano Letters
Swati Bagde, Vinod Singh
BACKGROUND: The Cellular immunity plays an important role in amoebic infections, whereas humoral immune responses have little influence on the outcome of the disease. Chronic infestation with E. histolytica, a common protozoan parasite, has been associated with autoimmune phenomena, including the appearance of antibodies to colonic epithelial cells. The mechanism whereby the protozoan parasite E. histolytica causes suppression of the immune response to allow it to survive in humans is unclear...
June 21, 2018: Recent Patents on Inflammation & Allergy Drug Discovery
Guangwei Xu, Tianqi Wang, Yongtao Li, Zhi Huang, Xin Wang, Jianyu Zheng, Shengyong Yang, Yan Fan, Rong Xiang
Indoleamine 2,3-dioxygenase 1 (IDO1) activity links to immune escape of cancers. Inhibition of IDO1 provides a new approach for cancer treatment. Most clinical IDO1 drugs show marginal efficacy as single agents. On basis of molecular docking and pharmacophore modelling, a novel inhibitor Roxyl-WL was discovered with a half maximal inhibitory concentration (IC50) value of 1 nM against IDO1 and 10-100-fold increased potent activity compared with IDO1 drugs in clinical trials. Roxyl-WL displayed excellent kinase spectrum selectivity with no activity out of the 337 protein kinases...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Lori A Ramkissoon, Nicholas Britt, Alexander Guevara, Emily Whitt, Eric Severson, Pratheesh Sathyan, Laurie Gay, Julia Elvin, Jeffrey S Ross, Charlotte Brown, Kimberly Stogner-Underwood, Ryan Mott, David Kram, Roy Strowd, Glenn J Lesser, Shakti H Ramkissoon
In recent years, large-scale genomic studies have expanded our knowledge regarding genomic drivers in tumors of the central nervous system. While histopathologic analysis of brain tumors remains the primary method for tumor classification, the clinical utility of molecular and genomic testing to support and/or complement tumor classification continues to expand. This approach enhances diagnostic accuracy and provides clinicians with objective data to facilitate discussions regarding prognosis and treatment decisions, including selection of clinical trials...
June 21, 2018: Current Treatment Options in Oncology
Satomi Kasashima, Atsuhiro Kawashima, Fuminori Kasashima, Masamitsu Endo, Yasushi Matsumoto, Kengo Kawakami
Immunoglobulin (IgG) 4-related diseases (IgG4-RDs) are fibro-inflammatory conditions characterized by tumorous swelling and serum IgG4 levels. Intrapelvic IgG4-RD has been subclassified according to the localization site and aortic shape as IgG4-related aortic aneurysms (IgG4-AAs), periaortitis (IgG4-PA), and retroperitoneal fibrosis (IgG4-RF). The IgG4-AA pathogenesis would involve interleukin (IL)-6 upregulation, and Th2-predominant and Treg-activated immune conditions. We characterized the features of intrapelvic IgG4-RD lesions, including presence of vascular lesions...
June 21, 2018: Heart and Vessels
Robert L Ferris, Nabil F Saba, Barbara J Gitlitz, Robert Haddad, Ammar Sukari, Prakash Neupane, John C Morris, Krzysztof Misiukiewicz, Julie E Bauman, Moon Fenton, Antonio Jimeno, Douglas R Adkins, Charles J Schneider, Assuntina G Sacco, Keisuke Shirai, Daniel W Bowles, Michael Gibson, Tobenna Nwizu, Raphael Gottardo, Kristi L Manjarrez, Gregory N Dietsch, James Kyle Bryan, Robert M Hershberg, Ezra E W Cohen
Importance: Immunotherapy for recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) is promising. The toll-like receptor 8 (TLR8) agonist motolimod may stimulate innate and adaptive immunity. Objective: To determine whether motolimod improves outcomes for R/M SCCHN when combined with standard therapy. Design, Setting, and Participants: The Active8 study was a multicenter, randomized, double-blind, placebo-controlled clinical trial enrolling adult patients (age ≥18 years) with histologically confirmed R/M SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx between October 2013 and August 2015...
June 21, 2018: JAMA Oncology
Banafshe Hosseini, Bronwyn S Berthon, Ahmad Saedisomeolia, Malcolm R Starkey, Adam Collison, Peter A B Wark, Lisa G Wood
BACKGROUND: Inflammation is associated with an increased risk of a range of chronic diseases. A diet high in fruit and vegetables may help to reduce inflammation, as fruit and vegetables are rich sources of antioxidants and other biologically active substances, which may improve immune function. OBJECTIVE: To summarize the evidence, we executed a systematic review and meta-analysis examining the effects of fruit and/or vegetable intake on inflammatory biomarkers and immune cells in humans with different diseases and conditions...
June 21, 2018: American Journal of Clinical Nutrition
Shane P Duggan, Catherine Garry, Fiona M Behan, Sinead Phipps, Hiromi Kudo, Murat Kirca, Abdul Zaheer, Sarah McGarrigle, John V Reynolds, Robert Goldin, Steve E Kalloger, David F Schaeffer, Aideen Long, Jessica Strid, Dermot Kelleher
Background & Aims: Effective therapeutic approaches are urgently required to tackle the alarmingly poor survival outcomes in esophageal adenocarcinoma (EAC) patients. EAC originates from within the intestinal-type metaplasia, Barrett's esophagus, a condition arising on a background of gastroesophageal reflux disease and associated inflammation. Methods: This study used a druggable genome small interfering RNA (siRNA) screening library of 6022 siRNAs in conjunction with bioinformatics platforms, genomic studies of EAC tissues, somatic variation data of EAC from The Cancer Genome Atlas data of EAC, and pathologic and functional studies to define novel EAC-associated, and targetable, immune factors...
2018: Cellular and Molecular Gastroenterology and Hepatology
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