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Immunogenic cell death

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https://www.readbyqxmd.com/read/28938609/pegylated-arginine-deiminase-can-modulate-tumor-immune-microenvironment-by-affecting-immune-checkpoint-expression-decreasing-regulatory-t-cell-accumulation-and-inducing-tumor-t-cell-infiltration
#1
Elena Brin, Katherine Wu, Hsin-Tze Lu, Yudou He, Zhaoming Dai, Wei He
PEGylated arginine deiminase (ADI-PEG 20) is being investigated in clinical studies in arginine auxotrophic cancers and is well-tolerated. The anti-tumor properties of ADI-PEG 20 have been extensively investigated - ADI-PEG 20 inhibits the growth of auxotrophic cancers in vitro and in vivo - however, its impact on immune cells is largely unknown. Here we report the potential impact of ADI-PEG 20 on the tumor immune microenvironment. ADI-PEG 20 induced immunosuppressive programmed death-ligand 1 expression on some cancer cells in vitro, but the magnitude of the increase was cell line dependent and in most relatively small...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938593/endoplasmic-reticulum-stress-mediated-membrane-expression-of-crt-erp57-induces-immunogenic-apoptosis-in-drug-resistant-endometrial-cancer-cells
#2
Qin Xu, Chuanben Chen, An Lin, Yunqing Xie
OBJECTIVE: To investigate the role of endoplasmic reticulum (ER) stress-mediated CRT/ERp57 complex expression underlying the mechanism of resistance to doxorubicin (DOX) in endometrial carcinoma (EC) in vivo and in vitro. METHODS: The expression of CRT, ERp57, p-PERK, eIF2α, p-eIF2α in EC patients and EC cells was detected by Western blots and by immunofluorescence assay. MTT assay was used to determine the LC50 of EC cells to DOX and cell viability. Apoptosis was assayed using flow cytometer...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28935111/evaluation-of-virus-like-particle-based-tumor-associated-carbohydrate-immunogen-in-a-mouse-tumor-model
#3
Suttipun Sungsuwan, Xuanjun Wu, Xuefei Huang
Tumor-associated carbohydrate antigens (TACAs) are attractive targets for anticancer vaccine development. Due to the low immunogenicity of TACAs, a powerful carrier system is needed to boost immune responses. Virus-like particles (VLPs) are an exciting platform for delivering TACAs to the immune system. The high symmetry of VLPs enables the display of TACAs in an organized manner, which in turn can potently activate antibody secreting B cells, eliciting high titers of antiglycan IgG antibodies. In this chapter, the protocol for conjugating a prototypical TACA, the Tn antigen to a VLP, bacteriophage Qβ, is presented...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28932647/immunotherapy-with-listeria-reduces-metastatic-breast-cancer-in-young-and-old-mice-through-different-mechanisms
#4
Arthee Jahangir, Dinesh Chandra, Wilber Quispe-Tintaya, Manisha Singh, Benson Chellakkan Selvanesan, Claudia Gravekamp
Cancer immunotherapy is one of the most promising and benign therapies against metastatic cancer. However, most cancer patients are old and elderly react less efficient to cancer vaccines than young adults, due to T cell unresponsiveness. Here we present data of cancer vaccination in young and old mice with metastatic breast cancer (4T1 model). We tested adaptive and innate immune responses to foreign antigens (Listeria-derived) and self-antigens (tumor-associated antigens (TAA)) and their contribution to elimination of metastases at young and old age...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28918908/macrophage-biology-plays-a-central-role-during-ionizing-radiation-elicited-tumor-response
#5
REVIEW
Qiuji Wu, Awatef Allouch, Isabelle Martins, Nazanine Modjtahedi, Eric Deutsch, Jean-Luc Perfettini
Radiation therapy is one of the major therapeutic modalities for most solid tumors. The anti-tumor effect of radiation therapy consists of the direct tumor cell killing, as well as the modulation of tumor microenvironment and the activation of immune response against tumors. Radiation therapy has been shown to promote immunogenic cells death, activate dendritic cells and enhance tumor antigen presentation and anti-tumor T cell activation. Radiation therapy also programs innate immune cells such as macrophages that leads to either radiosensitization or radioresistance, according to different tumors and different radiation regimen studied...
August 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28918474/induction-of-immunogenic-cell-death-in-lymphoma-cells-by-wharton-s-jelly-mesenchymal-stem-cell-conditioned-medium
#6
Daniel Hao Lin, Arijit Biswas, Mahesh Choolani, Chui-Yee Fong, Ariff Bongso
Strategies that induce immunogenic cell death (ICD) or downregulate CD47 or PD-L1 expression have resulted in successful therapeutic options for tumor eradication. Several groups have reported the tumoricidal effects of human umbilical cord Wharton's jelly stem cells (hWJSCs) or its conditioned medium (hWJSC-CM) on certain cancers but the mechanisms have not been elucidated. Since hWJSCs possess immunomodulatory properties, we investigated whether one of the tumoricidal mechanisms was via ICD. We first concentrated hWJSC-CM into a 3 kDa concentrate and then exposed various concentrations of this concentrate to human lymphoma cells to find out which concentration had the greatest tumoricidal effect...
September 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28917247/the-optimism-surrounding-stereotactic-body-radiation-therapy-and-immunomodulation
#7
Hannah Tharmalingam, Peter J Hoskin
In recent years, rapidly evolving radiation techniques have enabled the precise delivery of very high doses of radiation to local targets with stereotactic ablative body radiotherapy (SABR). In addition to its direct cytotoxicity, radiation and in particular SABR has powerful immunomodulatory effects resulting in immunogenic cell death and potentiation of the anti-tumour immune response. However, due to the immunosuppressive nature of non-irradiated sites of metastases, radiotherapy alone is seldom sufficient to induce the systemic response required for distant tumour rejection...
September 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28914317/a-bifunctional-nanomodulator-for-boosting-cpg-mediated-cancer-immunotherapy
#8
Zhenzhen Wang, Yan Zhang, Zhen Liu, Kai Dong, Chaoqun Liu, Xiang Ran, Fang Pu, Enguo Ju, Jinsong Ren, Xiaogang Qu
Unmethylated cytosine-phosphate-guanine (CpG) oligonucleotides (ODNs) possess high immunostimulatory activity and represent attractive tools for cancer treatment. However, their success in eliminating large solid tumors was hampered by the immunosuppressive tumor microenvironment. Herein, we report that the design of a novel MnO2-CpG-silver nanoclusters (AgNCs)-doxorubicin (DOX) conjugate for enhanced cancer immunotherapy, in which MnO2 nanosheets function as unique supports to integrate the chemotherapy drug DOX and the immunotherapeutic agent CpG-AgNCs...
September 15, 2017: Nanoscale
https://www.readbyqxmd.com/read/28914200/development-of-peptide-vaccines-in-dengue
#9
Kavita Reginald, Yanqi Chan, Magdalena Plebanski, Chit Laa Poh
Dengue is one of the most important arboviral infection worldwide, infecting up to 390 million people and causing 25,000 deaths annually. Although a licensed dengue vaccine is available, it is not efficacious against dengue serotypes that infect people living in South East Asia, where dengue is an endemic disease. Hence, there is an urgent need to develop an efficient dengue vaccine for this region. Data from different clinical trials indicate that a successful dengue vaccine must elicit both neutralizing antibodies and cell mediated immunity...
September 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28912395/-cytotoxic-agents-and-immune-checkpoint-inhibitors
#10
Akihito Kawazoe, Kohei Shitara
It has been reported that favorable influences of cytotoxic agents to anti-tumor immune response included immunogenic cell death and suppression of regulatory T cell and myeloid-derived suppressor cell. Some clinical trials showed that the addition of immune checkpoint inhibitor to standard chemotherapy improved efficacy in patients with non-small-cell lung cancer or malignant melanoma in first-line settings. Phase III trials of the combination of immune checkpoint inhibitor and chemotherapy in several malignancies are ongoing...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28900382/immunization-enhances-the-natural-antibody-repertoire
#11
Dylan Beinart, Daniel Ren, Cinthia Pi, Susan Poulton, Zoie E Holzknecht, Chelsea Swanson, William Parker
The role of immunization in the production of antibodies directed against immunogens is widely appreciated in laboratory animals and in humans. However, the role of immunization in the development of "natural antibodies" has not been investigated. Natural antibodies are those antibodies present without known history of infection or immunization, and react to a wide range of targets, including "cryptic" self-antigens that are exposed upon cell death. In this study, the ability of immunization to elicit the production of natural antibodies in laboratory rats was evaluated...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28893901/expression-of-pd-l1-in-hormone-na%C3%A3-ve-and-treated-prostate-cancer%C3%A2-patients-receiving-neoadjuvant%C3%A2-abiraterone-acetate-plus-prednisone-and-leuprolide
#12
Carla Calagua, Joshua Russo, Yue Sun, Rachel Schaefer, Rosina Lis, Zhenwei Zhang, Kathleen M Mahoney, Glenn J Bubley, Massimo Loda, Mary-Ellen Taplin, Steven P Balk, Huihui Ye
PURPOSE: Programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) blockade has been unsuccessful in prostate cancer (PCa), with poor immunogenicity and subsequent low PD-L1 expression in PCa being proposed as an explanation. However, recent studies indicate that a subset of PCa may express significant levels of PD-L1. Further, the androgen antagonist enzalutamide has been shown to up-regulate PD-L1 expression in PCa preclinical models. In this study, we evaluated the effect of neoadjuvant androgen deprivation therapy with abiraterone acetate plus prednisone and leuprolide (Neo-AAPL) on PD-L1 expression in PCa...
September 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28889919/emerging-immunotherapy-in-advanced-renal-cell-carcinoma
#13
REVIEW
Prateek Mendiratta, Brian I Rini, Moshe C Ornstein
Immunotherapy has recently catapulted to the forefront of treatments for patients with solid tumors. Given its inherent immunogenic properties, renal cell carcinoma (RCC) has historically responded to immunotherapy and remains primed for further development. Although immunotherapy with high-dose interleukin 2 was a primary treatment for advanced RCC (aRCC), recent discoveries of key molecular and immunological alterations have led to the FDA-approval of nivolumab, an antiprogrammed cell death inhibitor, which has demonstrated an overall survival in patients with previously treated aRCC...
September 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28883283/oncolytic-coxsackievirus-therapy-as-an-immunostimulator
#14
Shohei Miyamoto, Miyako Sagara, Hiroshi Kohara, Kenzaburo Tani
Recently, the active development of oncolytic virotherapy has gathered attention. Enterovirus research seeks to better understand its pathogenicity. In particular, coxsackievirus A21 (CVA21) is a promising candidate for oncolytic virotherapy, and thus is the focus of many clinical trials. We have reported that coxsackievirus B3 (CVB3) had potent oncolytic activity for cancer, and induced immunogenic cell death of CVB3-infected cells. We then genetically engineered wild type CVB3 and successfully produced a novel recombinant CVB3-miRT, improving its safety by the introducing an organ-specific miRNA target sequence...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28878015/thioredoxin-1-actively-maintains-the-pseudokinase-mlkl-in-a-reduced-state-to-suppress-disulfide-bond-dependent-mlkl-polymer-formation-and-necroptosis
#15
Eduardo Reynoso, Hua Liu, Lin Li, Anthony L Yuan, She Chen, Zhigao Wang
Necroptosis is an immunogenic cell death program that is associated with a host of human diseases, including inflammation, infections and cancer. Receptor-interacting protein kinase 3 (RIPK3) and its substrate mixed lineage kinase domain-like protein (MLKL) are required for necroptosis activation. Specifically, RIPK3-dependent MLKL phosphorylation promotes the assembly of disulfide bond-dependent MLKL polymers that drive the execution of necroptosis. However, how MLKL disulfide bond formation is regulated is not clear...
September 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28875845/new-trends-in-anti-cancer-therapy-combining-conventional-chemotherapeutics-with-novel-immunomodulators
#16
Amy L Wilson, Magdalena Plebanski, Andrew N Stephens
Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1...
August 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28867168/the-unfolded-protein-response-in-immunogenic-cell-death-and-cancer-immunotherapy
#17
REVIEW
Nicole Rufo, Abhishek D Garg, Patrizia Agostinis
The unfolded protein response (UPR) is a conserved pathway that is stimulated when endoplasmic reticulum (ER) proteostasis is disturbed or lost. Accumulating evidence indicates that chronic activation of the UPR supports the main hallmarks of cancer by favoring cancer cell-autonomous and nonautonomous processes, which ultimately foster the immunosuppressive and protumorigenic microenvironment. However, certain forms of therapy-induced ER stress can elicit immunogenic cancer cell death (ICD), which enables the release of key immunostimulatory or danger signals, eventually driving efficient antitumor immunity...
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28863168/a-novel-polyepitope-vaccine-elicited-hiv-peptide-specific-cd4-t-cell-responses-in-hla-a2-drb1-transgenic-mice
#18
Haitao Liu, Wei Shen, Jiayi Shu, Zhihua Kou, Xia Jin
Human immunodeficiency (HIV) infection is a leading global health problem that causes approximately one million deaths each year. Although antiretroviral therapy can slow down the disease progression and improve the quality of life of infected individuals, it cannot eradicate the virus. A successful vaccine is one of the most cost-effective alternatives to control the incidence and mortality of HIV infection. CD4+ T cells play a key role in orchestrating other forms of human immune responses, therefore, an HIV vaccine that includes a component capable of eliciting CD4+ T cell responses is highly desirable...
2017: PloS One
https://www.readbyqxmd.com/read/28857157/newcastle-disease-virus-mediates-pancreatic-tumor-rejection-via-nk-cell-activation-and-prevents-cancer-relapse-by-prompting-adaptive-immunity
#19
Theresa Schwaiger, Michael R Knittler, Christian Grund, Angela Roemer-Oberdoerfer, Joachim-Friedrich Kapp, Markus M Lerch, Thomas C Mettenleiter, Julia Mayerle, Ulrike Blohm
Pancreatic cancer is the 8(th) most common cause of cancer-related deaths worldwide and the tumor with the poorest prognosis of all solid malignancies. In 1957 it was discovered that Newcastle disease virus (NDV) has oncolytic properties on tumor cells. To study the oncolytic properties of NDV in pancreatic cancer a single dose was administered intravenously in a syngenic orthotopic tumor model employing two different murine pancreatic adenocarcinoma cell lines (DT6606PDA, Panc02). Tumor growth was monitored and immune response was analyzed...
August 31, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28856238/reovirus-fast-protein-enhances-vesicular-stomatitis-virus-oncolytic-virotherapy-in-primary-and-metastatic-tumor-models
#20
Fabrice Le Boeuf, Simon Gebremeskel, Nichole McMullen, Han He, Anna L Greenshields, David W Hoskin, John C Bell, Brent Johnston, Chungen Pan, Roy Duncan
The reovirus fusion-associated small transmembrane (FAST) proteins are the smallest known viral fusogens (∼100-150 amino acids) and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy. The oncolytic activity of recombinant VSVΔM51 (an interferon-sensitive vesicular stomatitis virus [VSV] mutant) encoding the p14 FAST protein (VSV-p14) was compared with a similar construct encoding GFP (VSV-GFP) in cell culture and syngeneic BALB/c tumor models...
September 15, 2017: Molecular Therapy Oncolytics
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