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Immunogenic cell death

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https://www.readbyqxmd.com/read/28507789/calreticulin-promotes-immunity-and-type-i-interferon-dependent-survival-in-mice-with-acute-myeloid-leukemia
#1
Xiufen Chen, Dominick Fosco, Douglas E Kline, Justin Kline
Exposure of cancer cells to particular chemotherapeutic agents or γ-irradiation induces a form of cell death that stimulates an immune response in mice. This "immunogenic cell death" requires calreticulin (CRT) translocation to the plasma membrane, which has been shown to promote cancer cell phagocytosis. However, it remains unclear whether the effect of CRT on cancer cell phagocytosis is alone sufficient to affect tumor immunity. Acute myeloid leukemia (AML) cells expressing cell-surface CRT were generated in order to characterize the mechanism(s) through which CRT activates tumor immune responses...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28498840/a-third-generation-vaccine-for-human-visceral-leishmaniasis-and-post-kala-azar-dermal-leishmaniasis-first-in-human-trial-of-chad63-kh
#2
Mohamed Osman, Anoop Mistry, Ada Keding, Rhian Gabe, Elizabeth Cook, Sarah Forrester, Rebecca Wiggins, Stefania Di Marco, Stefano Colloca, Loredana Siani, Riccardo Cortese, Deborah F Smith, Toni Aebischer, Paul M Kaye, Charles J Lacey
BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs...
May 12, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28496337/immunogenicity-of-oncolytic-vaccinia-viruses-jx-gfp-and-tg6002-in-a-human-melanoma-in-vitro-model-studying-immunogenic-cell-death-dendritic-cell-maturation-and-interaction-with-cytotoxic-t-lymphocytes
#3
B Heinrich, J Klein, M Delic, K Goepfert, V Engel, L Geberzahn, M Lusky, P Erbs, X Preville, M Moehler
Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP) and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) or transforming 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). We compared their properties to kill tumor cells and induce an immunogenic type of cell death in a human melanoma cell model using SK29-MEL melanoma cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28495513/high-hydrostatic-pressure-affects-antigenic-pool-in-tumor-cells-implication-for-dendritic-cell-based-cancer-immunotherapy
#4
Linda Urbanova, Nada Hradilova, Irena Moserova, Sarka Vosahlikova, Lenka Sadilkova, Michal Hensler, Radek Spisek, Irena Adkins
High hydrostatic pressure (HHP) can be used to generate dendritic cell (DC)-based active immunotherapy for prostate, lung and ovarian cancer. We showed here that HHP treatment of selected human cancer cell lines leads to a degradation of tumor antigens which depends on the magnitude of HHP applied and on the cancer cell line origin. Whereas prostate or ovarian cell lines displayed little protein antigen degradation with HHP treatment up to 300MPa after 2h, tumor antigens are hardly detected in lung cancer cell line after treatment with HHP 250MPa at the same time...
May 8, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28492558/harnessing-combined-p19arf-and-interferon-beta-gene-transfer-as-an-inducer-of-immunogenic-cell-death-and-mediator-of-cancer-immunotherapy
#5
Aline Hunger, Ruan Fv Medrano, Bryan E Strauss
No abstract text is available yet for this article.
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28476627/-the-impact-of-mycobacterium-tuberculosis-immune-evasion-on-protective-immunity-implications-for-tb-vaccine-design-meeting-report
#6
Cesar Boggiano, Katrin Eichelberg, Lakshmi Ramachandra, Jaqueline Shea, Lalita Ramakrishnan, Samuel Behar, Joel D Ernst, Steven A Porcelli, Markus Maeurer, Hardy Kornfeld
Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB...
May 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28469081/c3d-regulates-immune-checkpoint-blockade-and-enhances-antitumor-immunity
#7
Jeffrey L Platt, Inês Silva, Samuel J Balin, Adam R Lefferts, Evan Farkash, Ted M Ross, Michael C Carroll, Marilia Cascalho
Despite expression of immunogenic polypeptides, tumors escape immune surveillance by engaging T cell checkpoint regulators and expanding Tregs, among other mechanisms. What orchestrates these controls is unknown. We report that free C3d, a fragment of the third component of complement, inside tumor cells - or associated with irradiated tumor cells and unattached to antigen - recruits, accelerates, and amplifies antitumor T cell responses, allowing immunity to reverse or even to prevent tumor growth. C3d enhances antitumor immunity independently of B cells, NK cells, or antibodies, but it does so by increasing tumor infiltrating CD8+ lymphocytes, by depleting Tregs, and by suppressing expression of programmed cell death protein 1 (PD-1) by T cells...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28468914/rig-i-resists-hypoxia-induced-immunosuppression-and-dedifferentiation
#8
Christina Engel, Grethe Brügmann, Silke Lambing, Larissa H Mühlenbeck, Samira Marx, Christian Hagen, Dorottya Horváth, Marion Goldeck, Janos Ludwig, Anna-Maria Herzner, Jan W Drijfhout, Daniela Wenzel, Christoph Coch, Thomas Tüting, Martin Schlee, Veit Hornung, Gunther Hartmann, Jasper G Van den Boorn
A hypoxic tumor microenvironment is linked to poor prognosis. It promotes tumor cell dedifferentiation and metastasis and desensitizes tumor cells to type-I interferon (IFN), chemotherapy, and irradiation. The cytoplasmic immunoreceptor retinoic acid-inducible gene-I (RIG-I) is ubiquitously expressed in tumor cells and upon activation by 5'-triphosphate RNA (3pRNA) drives the induction of type I IFN and immunogenic cell death. Here, we analyzed the impact of hypoxia on the expression of RIG-I in various human and murine tumor and nonmalignant cell types and further investigated its function in hypoxic murine melanoma...
May 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28467380/nanosecond-pulsed-dbd-plasma-generated-reactive-oxygen-species-trigger-immunogenic-cell-death-in-a549-lung-carcinoma-cells-through-intracellular-oxidative-stress
#9
Abraham Lin, Billy Truong, Sohil Patel, Nagendra Kaushik, Eun Ha Choi, Gregory Fridman, Alexander Fridman, Vandana Miller
A novel application for non-thermal plasma is the induction of immunogenic cancer cell death for cancer immunotherapy. Cells undergoing immunogenic death emit danger signals which facilitate anti-tumor immune responses. Although pathways leading to immunogenic cell death are not fully understood; oxidative stress is considered to be part of the underlying mechanism. Here; we studied the interaction between dielectric barrier discharge plasma and cancer cells for oxidative stress-mediated immunogenic cell death...
May 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28465158/measles-virus-hemagglutinin-epitopes-immunogenic-in-natural-infection-and-vaccination-are-targeted-by-broad-or-genotype-specific-neutralizing-monoclonal-antibodies
#10
Miguel Angel Muñoz-Alía, José M Casasnovas, María Luisa Celma, Juan Carabaña, Paloma B Liton, Rafael Fernandez-Muñoz
Measles virus (MV) remains a leading cause of vaccine-preventable deaths in children. Protection against MV is associated with neutralizing antibodies that preferentially recognize the viral hemagglutinin (MV-H), and to a lesser extent, the fusion protein (MV-F). Although MV is serologically monotypic, 24 genotypes have been identified. Here we report three neutralization epitopes conserved in the more prevalent circulating MV genotypes, two located in the MV-H receptor binding site (RBS) (antigenic site III) and a third in MV-H/MV-F interphase (antigenic site Ia)...
April 29, 2017: Virus Research
https://www.readbyqxmd.com/read/28463396/t-cell-infiltration-and-clonality-correlate-with-programmed-cell-death-protein-1-and-programmed-death-ligand-1-expression-in-patients-with-soft-tissue-sarcomas
#11
Seth M Pollack, Qianchuan He, Jennifer H Yearley, Ryan Emerson, Marissa Vignali, Yuzheng Zhang, Mary W Redman, Kelsey K Baker, Sara Cooper, Bailey Donahue, Elizabeth T Loggers, Lee D Cranmer, Matthew B Spraker, Y David Seo, Venu G Pillarisetty, Robert W Ricciotti, Benjamin L Hoch, Terrill K McClanahan, Erin Murphy, Wendy M Blumenschein, Steven M Townson, Sharon Benzeno, Stanley R Riddell, Robin L Jones
BACKGROUND: Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited. METHODS: The authors identified patients with the common STS subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), well-differentiated/dedifferentiated liposarcoma, and myxoid/round cell liposarcoma. Gene expression, immunohistochemistry for programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), and T-cell receptor Vβ gene sequencing were performed on formalin-fixed, paraffin-embedded tumors from 81 patients...
May 2, 2017: Cancer
https://www.readbyqxmd.com/read/28457491/chemoimmunotherapeutic-effect-of-combined-treatment-with-ex-vivo-generated-antigen-presenting-immune-cells-and-conventional-antitumor-agents-in-a-mouse-neuroblastoma-model
#12
Seiichiro Inoue, Yumiko Setoyama, Akio Odaka, Daiki Kitagawa, Yoshifumi Beck
PURPOSE: Combining antitumor immunotherapy with conventional intensive multimodal therapy may be considered for advanced neuroblastoma. We investigated combination therapy with ex vivo generated immunostimulatory cells and intraperitoneal doxorubicin. METHODS: Immunogenic death of neuro-2a neuroblastoma cells was induced by doxorubicin or cisplatin (negative control). Mouse bone marrow cells were cultured with granulocyte-macrophage colony-stimulating factor, followed by addition of doxorubicin-killed neuro-2a cells with or without interleukin-4 and/or CpG-oligodeoxynucleotide to induce immunostimulatory cells...
April 21, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28453702/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#13
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E M Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28446053/immunotherapy-for-the-treatment-of-breast-cancer
#14
Mariela A Moreno Ayala, Maria Florencia Gottardo, Antonela S Asad, Camila Zuccato, Alejandro Nicola, Adriana Seilicovich, Marianela Candolfi
Breast cancer is the most common cancer as well as the first cause of death by cancer in women worldwide. Although routine treatment improves the outcome of early stage breast cancer patients, there is no effective therapy for the disseminated disease. Immunotherapy has emerged as a powerful therapeutic strategy for the treatment of many cancers. Although traditionally conceived as a non-immunogenic tumor, breast cancer is now considered a potential target for immunotherapy. Areas covered: In this review, the authors discuss different immunotherapeutic strategies that are currently being tested for the treatment of breast cancer: These strategies include: (i) blockade of immunological checkpoints, (ii) antitumor vaccines, (iii) regulatory T cell blockade, (iv) adoptive T cell transfer therapy, (iv) adoptive immunotherapy with monoclonal antibodies, and (v) combination of immunotherapy with chemotherapy...
May 8, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#15
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28430664/identification-of-a-novel-pd-l1-positive-solid-tumor-transplantable-in-hla-a-0201-drb1-0101-transgenic-mice
#16
Laurie Rangan, Jeanne Galaine, Romain Boidot, Mohamad Hamieh, Magalie Dosset, Julie Francoual, Laurent Beziaud, Jean-René Pallandre, Elodie Lauret Marie Joseph, Afag Asgarova, Christophe Borg, Talal Al Saati, Yann Godet, Jean Baptiste Latouche, Séverine Valmary-Degano, Olivier Adotévi
HLA-A*0201/DRB1*0101 transgenic mice (A2/DR1 mice) have been developed to study the immunogenicity of tumor antigen-derived T cell epitopes. To extend the use and application of this mouse model in the field of antitumor immunotherapy, we described a tumor cell line generated from a naturally occurring tumor in A2/DR1 mouse named SARC-L1. Histological and genes signature analysis supported the sarcoma origin of this cell line. While SARC-L1 tumor cells lack HLA-DRB1*0101 expression, a very low expression of HLA-A*0201 molecules was found on these cells...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428881/nano-pulse-stimulation-is-a-physical-modality-that-can-trigger-immunogenic-tumor-cell-death
#17
Richard Nuccitelli, Amanda McDaniel, Snjezana Anand, John Cha, Zachary Mallon, Jon Casey Berridge, Darrin Uecker
BACKGROUND: We have been developing a non-thermal, drug-free tumor therapy called Nano-Pulse Stimulation (NPS) that delivers ultrashort electric pulses to tumor cells which eliminates the tumor and inhibits secondary tumor growth. We hypothesized that the mechanism for inhibiting secondary tumor growth involves stimulating an adaptive immune response via an immunogenic form of apoptosis, commonly known as immunogenic cell death (ICD). ICD is characterized by the emission of danger-associated molecular patterns (DAMPs) that serve to recruit immune cells to the site of the tumor...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28427861/divergent-function-of-programmed-death-ligand-1-in-donor-tissue-versus-recipient-immune-system-in-a-murine-model-of-bronchiolitis-obliterans
#18
Katharina Schütte-Nütgen, Olaf Boenisch, Hakima Harrach, Alicia Casey, Indira Guleria, Nader Najafian, Mohamed H Sayegh, Craig J Gerard, Meera Subramaniam
Costimulatory molecules, such as the programmed death ligand (PD-L1), might exert differential effects on T-cell function, depending on the clinical setting and/or immunological environment. Given the impact of T cells on bronchiolitis obliterans (BO) in lung transplantation, we used an established tracheal transplant model inducing BO-like lesions to investigate the impact of PD-L1 on alloimmune responses and histopathological outcome in BO. In contrast to other transplant models in which PD-L1 generally shows protective functions, we demonstrated that PD-L1 has divergent effects depending on its location in donor versus recipient tissue...
June 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28427434/adenovirus-mediated-cd40l-gene-transfer-increases-teffector-tregulatory-cell-ratio-and-upregulates-death-receptors-in-metastatic-melanoma-patients
#19
A Schiza, J Wenthe, S Mangsbo, E Eriksson, Anders Nilsson, T H Tötterman, A Loskog, G Ullenhag
BACKGROUND AND AIMS: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). METHODS: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide...
April 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28409192/can-local-radiotherapy-and-il-12-synergise-to-overcome-the-immunosuppressive-tumor-microenvironment-and-allow-in-situ-tumor-vaccination
#20
Gaël Deplanque, Keyvan Shabafrouz, Michel Obeid
The abscopal effect, which is the spontaneous regression of tumors or metastases outside the radiation field, occurs rarely in cancer patients. Interestingly, radiotherapy (RT) triggers an immunogenic cell death (ICD) that is able to generate tumor-specific cytotoxic CD8(+) T cells that are efficient in killing cancer cells. The key question is: why is this "abscopal effect" so uncommon in cancer patients treated with RT? Most probably, the main reason may be related to the highly immunosuppressive tumor microenvironment of well-established tumors that constantly antagonizes the anti-tumor immune responses triggered by RT...
April 13, 2017: Cancer Immunology, Immunotherapy: CII
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