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Tumor priming

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https://www.readbyqxmd.com/read/29331266/human-papilloma-virus-specific-t-cells-can-be-generated-from-na%C3%A3-ve-t-cells-for-use-as-an-immunotherapeutic-strategy-for-immunocompromised-patients
#1
Sarah E McCormack, Conrad Russell Y Cruz, Kaylor E Wright, Allison B Powell, Haili Lang, Cornelia Trimble, Michael D Keller, Ephraim Fuchs, Catherine M Bollard
Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. Although treatments exist for HPV-associated malignancies, patients unresponsive to these therapies have a poor prognosis. Recent findings from vaccine studies suggest that T-cell immunity is essential for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing platform for HPV-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers...
January 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29324702/listeria-monocytogenes-the-impact-of-cell-death-on-infection-and-immunity
#2
REVIEW
Courtney E McDougal, John-Demian Sauer
Listeria monocytogenes has evolved exquisite mechanisms for invading host cells and spreading from cell-to-cell to ensure maintenance of its intracellular lifecycle. As such, it is not surprising that loss of the intracellular replication niche through induction of host cell death has significant implications on the development of disease and the subsequent immune response. Although L. monocytogenes can activate multiple pathways of host cell death, including necrosis, apoptosis, and pyroptosis, like most intracellular pathogens L...
January 11, 2018: Pathogens
https://www.readbyqxmd.com/read/29310916/chimeric-antigen-receptor-engineered-human-gamma-delta-t-cells-enhanced-cytotoxicity-with-retention-of-cross-presentation
#3
Anna Capsomidis, Gabriel Benthall, Heleen H Van Acker, Jonathan Fisher, Anne M Kramer, Zarah Abeln, Yvonne Majani, Talia Gileadi, Rebecca Wallace, Kenth Gustafsson, Barry Flutter, John Anderson
Gamma delta T (γδT) lymphocytes are primed for rapid function, including cytotoxicity toward cancer cells, and are a component of the immediate stress response. Following activation, they can function as professional antigen-presenting cells. Chimeric antigen receptors (CARs) work by focusing T cell function on defined cell surface tumor antigens and provide essential costimulation for robust activation. Given the natural tropism of γδT cells for the tumor microenvironment, we hypothesized that their transduction with CARs might enhance cytotoxicity while retaining their ability to migrate to tumor and act as antigen-presenting cells to prolong the intratumoral immune response...
December 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29298869/intravenous-delivery-of-oncolytic-reovirus-to-brain-tumor-patients-immunologically-primes-for-subsequent-checkpoint-blockade
#4
Adel Samson, Karen J Scott, David Taggart, Emma J West, Erica Wilson, Gerard J Nuovo, Simon Thomson, Robert Corns, Ryan K Mathew, Martin J Fuller, Timothy J Kottke, Jill M Thompson, Elizabeth J Ilett, Julia V Cockle, Philip van Hille, Gnanamurthy Sivakumar, Euan S Polson, Samantha J Turnbull, Elizabeth S Appleton, Gemma Migneco, Ailsa S Rose, Matthew C Coffey, Deborah A Beirne, Fiona J Collinson, Christy Ralph, D Alan Anthoney, Christopher J Twelves, Andrew J Furness, Sergio A Quezada, Heiko Wurdak, Fiona Errington-Mais, Hardev Pandha, Kevin J Harrington, Peter J Selby, Richard G Vile, Stephen D Griffin, Lucy F Stead, Susan C Short, Alan A Melcher
Immune checkpoint inhibitors, including those targeting programmed cell death protein 1 (PD-1), are reshaping cancer therapeutic strategies. Evidence suggests, however, that tumor response and patient survival are determined by tumor programmed death ligand 1 (PD-L1) expression. We hypothesized that preconditioning of the tumor immune microenvironment using targeted, virus-mediated interferon (IFN) stimulation would up-regulate tumor PD-L1 protein expression and increase cytotoxic T cell infiltration, improving the efficacy of subsequent checkpoint blockade...
January 3, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29298343/epcam-peptide-primed-dendritic-cell-vaccination-confers-significant-anti-tumor-immunity-in-hepatocellular-carcinoma-cells
#5
Yoo Jin Choi, Seong-Joon Park, You-Soo Park, Hee Sung Park, Kwang Mo Yang, Kyu Heo
Cancer stem-like cells (CSCs) may play a key role in tumor initiation, self-renewal, differentiation, and resistance to current treatments. Dendritic cells (DCs) play a vital role in host immune reactions as well as antigen presentation. In this study, we explored the suitability of using CSC peptides as antigen sources for DC vaccination against human breast cancer and hepatocellular carcinoma (HCC) with the aim of achieving CSC targeting and enhancing anti-tumor immunity. CD44 is used as a CSC marker for breast cancer and EpCAM is used as a CSC marker for HCC...
2018: PloS One
https://www.readbyqxmd.com/read/29297707/first-line-vascular-endothelial-growth-factor-targeted-therapy-in-renal-cell-carcinoma-priming-the-tumor-microenvironment-for-immunotherapy
#6
Nizar Tannir, Hans Hammers, Asim Amin
Despite improved outcomes with systemic vascular endothelial growth factor (VEGF)-targeted agents in patients with advanced renal cell carcinoma (RCC), the majority of patients will eventually develop treatment resistance and disease progression. With the emergence of checkpoint inhibitors as potential treatment approaches, studies suggest that ideally combining or sequencing them with VEGF receptor (VEGFR)-tyrosine kinase inhibitors (TKIs) may provide more effective treatments that reduce or delay disease progression...
January 3, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29296731/human-and-murine-splenic-neutrophils-are-potent-phagocytes-of-igg-opsonized-red-blood-cells
#7
Sanne M Meinderts, Per-Arne Oldenborg, Boukje M Beuger, Thomas R L Klei, Johanna Johansson, Taco W Kuijpers, Takashi Matozaki, Elise J Huisman, Masja de Haas, Timo K van den Berg, Robin van Bruggen
Red blood cell (RBC) clearance is known to occur primarily in the spleen, and is presumed to be executed by red pulp macrophages. Erythrophagocytosis in the spleen takes place as part of the homeostatic turnover of RBCs to remove old RBCs. It can be strongly promoted by immunoglobulin G (IgG) opsonization of RBCs, a condition that can occur as a consequence of autoantibody or alloantibody formation. The purpose of our study was to investigate which phagocytes are involved in IgG-mediated RBC clearance in the human spleen...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288681/resistance-to-receptor-blocking-therapies-primes-tumors-as-targets-for-her3-homing-nanobiologics
#8
Jessica D Sims, Jan Michael Taguiam, Felix Alonso-Valenteen, Janet Markman, Hasmik Agadjanian, David Chu, Jay Lubow, Ravinder Abrol, Dustin Srinivas, Anjali Jain, Bingchen Han, Ying Qu, Parisa Mirzadehgan, Jae-Youn Hwang, Altan Rentsendorj, Alice Chung, Jenny Lester, Beth Y Karlan, Harry B Gray, Zeev Gross, Armando Giuliano, Xiaojiang Cui, Lali K Medina-Kauwe
Resistance to anti-tumor therapeutics is an important clinical problem. Tumor-targeted therapies currently used in the clinic are derived from antibodies or small molecules that mitigate growth factor activity. These have improved therapeutic efficacy and safety compared to traditional treatment modalities but resistance arises in the majority of clinical cases. Targeting such resistance could improve tumor abatement and patient survival. A growing number of such tumors are characterized by prominent expression of the human epidermal growth factor receptor 3 (HER3) on the cell surface...
December 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29285747/potential-role-of-ndrg2-in-reprogramming-cancer-metabolism-and-epithelial-to-mesenchymal-transition
#9
REVIEW
Xiang-Liu Chen, Lan Lei, Lian-Lian Hong, Lian-Lian Ling
Epithelial-to-mesenchymal transition (EMT) allows a cell with epithelial characteristics to transdifferentiate into a cell with mesenchymal characteristics, which is recognized as a key priming event for the initiation and evolvement of cancer metastasis. Accumulating data have shown that aberrant cancer metabolism contributes to the execution of EMT and cancer metastasis through multiple pathological pathways. Recently, the N-MYC downstream-regulated gene 2 (NDRG2), as a tumor suppressor and metabolism-related gene in various cancers, has been widely noted...
December 29, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/29282521/engineered-exosomes-emerging-from-muscle-cells-break-immune-tolerance-to-her2-in-transgenic-mice-and-induce-antigen-specific-ctls-upon-challenge-by-human-dendritic-cells
#10
Simona Anticoli, Eleonora Aricò, Claudia Arenaccio, Francesco Manfredi, Chiara Chiozzini, Eleonora Olivetta, Flavia Ferrantelli, Laura Lattanzi, Maria Teresa D'Urso, Enrico Proietti, Maurizio Federico
We recently described a novel biotechnological platform for the production of unrestricted cytotoxic T lymphocyte (CTL) vaccines. It relies on in vivo engineering of exosomes, i.e., nanovesicles constitutively released by all cells, with full-length antigens of choice upon fusion with an exosome-anchoring protein referred to as Nefmut. They are produced upon intramuscular injection of a DNA vector and, when uploaded with a viral tumor antigen, were found to elicit an immune response inhibiting the tumor growth in a model of transplantable tumors...
December 27, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29281272/deformable-hollow-periodic-mesoporous-organosilica-nanocapsules-for-significantly-improved-cellular-uptake
#11
Zhaogang Teng, Chunyan Wang, Yuxia Tang, Wei Li, Lei Bao, Xuehua Zhang, Xiaodan Su, Fan Zhang, Junjie Zhang, Shouju Wang, Dongyuan Zhao, Guangming Lu
Mesoporous solids have been widely used in various biomedical areas such as drug delivery and tumor therapy. Although deformability has been recognized as a prime important characteristic influencing cellular uptake, the synthesis of deformable mesoporous solids is still a great challenge. Herein, deformable thioether-, benzene-, and ethane-bridged hollow periodic mesoporous organosilica (HPMO) nanocapsules have successfully been synthesized for the first time by a preferential etching approach. The prepared HPMO nanocapsules possess uniform diameters (240-310 nm), high surface areas (up to 878 m2g-1), well-defined mesopores (2...
December 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29275462/cancer-immunotherapy-targets-based-on-understanding-the-t-cell-inflamed-versus-non-t-cell-inflamed-tumor-microenvironment
#12
Thomas F Gajewski, Leticia Corrales, Jason Williams, Brendan Horton, Ayelet Sivan, Stefani Spranger
Most cancers express tumor antigens that can be recognized by T cells of the host. The fact that cancers become clinically evident nonetheless implies that immune escape must occur. Two major subsets of human melanoma metastases have been identified based on gene expression profiling. One subgroup has a T cell-inflamed phenotype that includes expression of chemokines, T cell markers, and a type I IFN signature. In contrast, the other major subset lacks this phenotype and has been designated as non-T cell-inflamed...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29273394/sting-dcs-and-the-link-between-innate-and-adaptive-tumor-immunity
#13
Ralph E Vatner, Edith M Janssen
Cancer and the immune system are intimately related. Much of the bulk of tumors is comprised of stromal leukocytes with immune functions, which serve to both promote and inhibit tumor growth, invasion and metastasis. The T lymphocytes of the adaptive immune system are essential for tumor immunity, and these T cells are generated by cross-priming against tumor associated antigens. Dendritic cells (DCs) are essential in this process, serving as the cellular link between innate and adaptive immunity. As a prerequisite for priming of adaptive immune responses, DCs must take up tumor antigens, process them and present them in the context of the major histocompatibility complex (MHC)...
December 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29273372/preischemic-transfusion-of-old-packed-rbcs-exacerbates-early-phase-warm-hepatic-ischemia-reperfusion-injury-in-rats
#14
Eun Kyung Choi, Jongyoon Baek, Sangyoung Park, Suk Hwan Baek, Joon-Hyuk Choi, Chae Hoon Lee, Eon-Gi Sung, Daelim Jee
BACKGROUND: Hepatic innate immune cells are considered to play a central role in the early phase of hepatic ischemia reperfusion (IR) injury. Transfusion of old red blood cells (RBCs) is known to prime immune cells, and transfusion before IR may exacerbate liver injury because of the expected hyperresponsiveness of immune cells. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were divided into four groups: sham operation (Sham); hepatic IR only (IR Control); and two transfusion groups, preischemic (Pre-T) and postischemic (Post-T), in which allogeneic RBCs stored for 2 weeks were transfused before hepatic IR or after reperfusion, respectively...
February 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29261410/cross-talk-between-radiation-and-immunotherapy-the-twain-shall-meet
#15
Swaminathan P Iyer, Clayton R Hunt, Tej K Pandita
There has been increased interest in the immune stimulatory properties of ionizing radiation based on several preclinical models and recently completed clinical studies performed in combination with checkpoint inhibitors. This is a paradigm shift in that it considers the role of radiation beyond its direct cytotoxic effects, however, the factors that promote or limit radiation-induced immunogenicity are still unclear. Here we review the role of radiation in modulating the various aspects of the tumor immune microenvironment and discuss in particular the direct effects of radiation on the DNA damage response and its immediate consequences to neighboring cells...
December 20, 2017: Radiation Research
https://www.readbyqxmd.com/read/29258605/mir-105-93-3p-promotes-chemoresistance-and-circulating-mir-105-93-3p-acts-as-a-diagnostic-biomarker-for-triple-negative-breast-cancer
#16
Hao-Yi Li, Jui-Lin Liang, Yao-Lung Kuo, Hao-Hsien Lee, Marcus J Calkins, Hong-Tai Chang, Forn-Chia Lin, Yu-Chia Chen, Tai-I Hsu, Michael Hsiao, Luo-Ping Ger, Pei-Jung Lu
BACKGROUND: Triple negative breast cancer (TNBC) lacks both early detection biomarkers and viable targeted therapeutics. Moreover, chemotherapy only produces 20-30% pathologic complete response. Because miRNAs are frequently dysregulated in breast cancer and have broad tissue effects, individual or combinations of circulating miRNAs may serve as ideal diagnostic, predictive or prognostic biomarkers, as well as therapeutic targets. Understanding the role and mechanism of dysregulated miRNAs in TNBC may help to develop novel diagnostic and prognostic strategy for TNBC patients...
December 19, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29258553/prenatal-alcohol-exposure-is-a-risk-factor-for-adult-neuropathic-pain-via-aberrant-neuroimmune-function
#17
Joshua J Sanchez, Shahani Noor, Suzy Davies, Daniel Savage, Erin D Milligan
BACKGROUND: Clinical studies show that prenatal alcohol exposure (PAE) results in effects that persist into adulthood. Experimental animal models of moderate PAE demonstrate that young adults with PAE display potentiated sensitivity to light touch, clinically termed allodynia, following sciatic nerve chronic constriction injury (CCI) that coincides with heightened spinal glial, spinal macrophage, and peripheral immune responses. However, basal touch sensitivity and corresponding glial and leukocyte activation are unaltered...
December 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29247341/from-biomarkers-to-therapeutic-targets-the-promises-and-perils-of-long-non-coding-rnas-in-cancer
#18
Tony Gutschner, Georg Richtig, Monika Haemmerle, Martin Pichler
Biomarker-driven personalized cancer therapy is a field of growing interest, and several molecular tests have been developed to detect biomarkers that predict, e.g., response of cancers to particular therapies. Identification of these molecules and understanding their molecular mechanisms is important for cancer prognosis and the development of therapeutics for late stage diseases. In the past, significant efforts have been placed on the discovery of protein or DNA-based biomarkers while only recently the class of long non-coding RNA (lncRNA) has emerged as a new category of biomarker...
December 15, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29245049/effects-of-priming-with-cytokines-on-intracellular-survival-and-replication-of-rhodococcus-equi-in-equine-macrophages
#19
Londa J Berghaus, Steeve Giguère, Angela I Bordin, Noah D Cohen
Rhodococcus equi is a common cause of pneumonia in foals and an opportunistic pathogen in immunosuppressed people. The ability of R. equi to survive and replicate in macrophages is the basis of its pathogenicity. Limited knowledge about the role of cytokines in host defense against R. equi comes from studies in mice and the role of cytokines in intracellular survival of R. equi in equine macrophages is unknown. The objectives of this study were to determine the effect of priming with interferon (IFN)-γ, interleukin (IL)-1β, IL-4, IL-6, IL-10, or tumor necrosis factor (TNF)-α at various concentrations on intracellular survival of virulent R...
December 12, 2017: Cytokine
https://www.readbyqxmd.com/read/29239144/smg-1-inhibition-by-mir-192-215-causes-epithelial-mesenchymal-transition-in-gastric-carcinogenesis-via-activation-of-wnt-signaling
#20
Xiaojing Zhang, Yin Peng, Yong Huang, Mengting Yang, Ruibin Yan, Yanqiu Zhao, Yulan Cheng, Xi Liu, Shiqi Deng, Xianling Feng, Huijuan Lin, Huimin Yu, Si Chen, Zhenfu Zhao, Shanni Li, Kuan Li, Liang Wang, Yanjie Wei, Zhendan He, Xinmin Fan, Stephen J Meltzer, Song Li, Zhe Jin
SMG-1,a member of the phosphoinositide kinase-like kinase family, functioned as a tumor suppressor gene. However, the role of SMG-1 in GC remain uncharacterized. In this study, regulation of SMG-1 by miR-192 and-215, along with the biological effects of this modulation, were studied in GC. We used gene microarrays to screening and luciferase reporter assays were to verify the potential targets of miR-192 and-215. Tissue microarrays analyses were applied to measure the levels of SMG-1 in GC tissues. Western blot assays were used to assess the signaling pathway of SMG-1 regulated by miR-192 and-215 in GC...
December 13, 2017: Cancer Medicine
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