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tumor induced immune suppression

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https://www.readbyqxmd.com/read/29456539/generation-of-human-immunosuppressive-myeloid-cell-populations-in-human-interleukin-6-transgenic-nog-mice
#1
Asami Hanazawa, Ryoji Ito, Ikumi Katano, Kenji Kawai, Motohito Goto, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi
The tumor microenvironment contains unique immune cells, termed myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that suppress host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although these cells are considered a key target of cancer immune therapy, in vivo animal models allowing differentiation of human immunosuppressive myeloid cells have yet to be established, hampering the development of novel cancer therapies. In this study, we established a novel humanized transgenic (Tg) mouse strain, human interleukin (hIL)-6-expressing NOG mice (NOG-hIL-6 transgenic mice)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29453519/tricurin-a-synergistic-formulation-of-curcumin-resveratrol-and-epicatechin-gallate-repolarizes-tumor-associated-macrophages-and-triggers-an-immune-response-to-cause-suppression-of-hpv-tumors
#2
Sumit Mukherjee, Rahman Hussaini, Richard White, Doaa Atwi, Angela Fried, Samay Sampat, Longzhu Piao, Quintin Pan, Probal Banerjee
Our earlier studies reported a unique potentiated combination (TriCurin) of curcumin (C) with two other polyphenols. The TriCurin-associated C displays an IC50 in the low micromolar range for cultured HPV+ TC-1 cells. In contrast, because of rapid degradation in vivo, the TriCurin-associated C reaches only low nano-molar concentrations in the plasma, which are sub-lethal to tumor cells. Yet, injected TriCurin causes a dramatic suppression of tumors in TC-1 cell-implanted mice (TC-1 mice) and xenografts of Head and Neck Squamous Cell Carcinoma (HNSCC) cells in nude/nude mice...
February 16, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29452101/socs3-deficiency-in-myeloid-cells-promotes-retinal-degeneration-and-angiogenesis-through-arginase-1-up-regulation-in-experimental-autoimmune-uveoretinitis
#3
Mei Chen, Jiawu Zhao, Imran Ha Ali, Stephen Marry, Josy Augustine, Mohajeet Bhuckory, Aisling Lynch, Adrien Kissenpfennig, Heping Xu
The suppressor of cytokine signalling protein 3 (SOCS3) critically controls immune cell activation, although its role in macrophage polarization and function remains controversial. Using experimental autoimmune uveoretinitis (EAU) as a model, we show that inflammation-mediated retinal degeneration is exaggerated and retinal angiogenesis is accelerated in mice with SOCS3 deficiency in myeloid cells (LysM Cre/+ SOCS3 fl/fl ). At the acute stage of EAU, the population of infiltrating neutrophils was increased and the population of macrophages decreased in LysM Cre/+ SOCS3 fl/fl mice compared to that in WT mice...
February 13, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29445008/blockade-of-host-%C3%AE-2-adrenergic-receptor-enhances-graft-versus-tumor-effect-through-modulating-apcs
#4
Hemn Mohammadpour, Rachel O'Neil, Jingxin Qiu, Philip L McCarthy, Elizabeth A Repasky, Xuefang Cao
Allogeneic hematopoietic cell transplantation is a potential curative therapy for hematologic malignancies. Host APCs are pivotal to the desired graft-versus-tumor (GVT) effect. Recent studies have shown that β2-adrenergic receptor (β2AR) signaling can have an important impact on immune cell function, including dendritic cells (DCs). In this article, we demonstrate that pretreatment of host mice with a β2AR blocker significantly increases the GVT effect of donor CD8 + T cells by decreasing tumor burden without increasing graft-versus-host disease...
February 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29439258/bone-marrow-cell-therapy-on-1-2-dimethylhydrazine-dmh-induced-colon-cancer-in-rats
#5
Manal F El-Khadragy, Heba M Nabil, Basmaa N Hassan, Amany A Tohamy, Hanaa F Waaer, Hany M Yehia, Afra M Alharbi, Ahmed Esmat Abdel Moneim
BACKGROUND/AIMS: Stem cell based therapies are being under focus due to their possible role in treatment of various tumors. Bone marrow stem cells believed to have anticancer potential and are preferred for their activities by stimulating the immune system, migration to the site of tumor and ability for inducting apoptosis in cancer cells. The current study was aimed to investigate the tumor suppressive effects of bone marrow cells (BMCs) in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats...
February 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29438328/dna-tumor-virus-regulation-of-host-dna-methylation-and-its-implications-for-immune-evasion-and-oncogenesis
#6
REVIEW
Sharon K Kuss-Duerkop, Joseph A Westrich, Dohun Pyeon
Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus-host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development...
February 13, 2018: Viruses
https://www.readbyqxmd.com/read/29438179/a-novel-small-molecular-stat3-inhibitor-5br-6b-induces-apoptosis-and-inhibits-migration-in-colorectal-cancer-cells
#7
Zhe Liu, Huan Wang, Lingnan Guan, Siyi Chen, Maode Lai
Signal transducers and activators of transcription 3 (STAT3) represent a transcription factor that is constitutively activated in various cancers. Numerous studies have shown that STAT3 plays crucial roles in cell proliferation and survival, angiogenesis, tumor-promoting inflammation, and suppression of antitumor host immune response in the tumor microenvironment. In this study, we investigated a novel inhibitor, called -6b, to target STAT3 in colorectal cancer cells. The influence of 5Br-6b on the proliferation of colorectal cell lines SW480 and HCT116 was evaluated using an 3-(4, 5-dimethylthiazolyl)-2 and 5-diphenyltetrazolium bromide assay...
February 12, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29436395/myeloid-targeted-immunotherapies-act-in-synergy-to-induce-inflammation-and-antitumor-immunity
#8
Curtis J Perry, Andrés R Muñoz-Rojas, Katrina M Meeth, Laura N Kellman, Robert A Amezquita, Durga Thakral, Victor Y Du, Jake Xiao Wang, William Damsky, Alexandra L Kuhlmann, Joel W Sher, Marcus Bosenberg, Kathryn Miller-Jensen, Susan M Kaech
Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge in cancer immunotherapy, and in such patients, tumor-associated myeloid cells and macrophages (TAMs) are promising therapeutic targets. We demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single cells identified that untreated tumors have distinct TAM subpopulations secreting MMP9 or cosecreting CCL17/22, characteristic of an M2-like state...
February 7, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29435073/effects-of-thalidomide-on-growth-and-vegf-a-expression-in-sw480-colon-cancer-cells
#9
Xin Zhang, Hesheng Luo
Lymphatic and hematogenous spread are the most common ways for tumors to metastasize. Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) particularly VEGF-A is important in the process of angiogenesis. The current research has indicated that thalidomide (THD) may be able to inhibit angiogenesis, stimulate the activity of the immune system and inhibit the adherence of cancer cells to stromal cells. These changes may lead to suppression of tumor occurrence and development...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434589/modeling-human-antitumor-responses-in-vivo-using-umbilical-cord-blood-engrafted-mice
#10
REVIEW
Nicholas A Zumwalde, Jenny E Gumperz
Mice engrafted with human immune cells offer powerful in vivo model systems to investigate molecular and cellular processes of tumorigenesis, as well as to test therapeutic approaches to treat the resulting cancer. The use of umbilical cord blood mononuclear cells as a source of human immune cells for engraftment is technically straightforward, and provides T lymphocytes and autologous antigen-presenting cells (including B cells, monocytes, and DCs) that bear cognate antigen presenting molecules. By using a human-specific oncogenic virus, such as Epstein-Barr virus, de novo neoplastic transformation of the human B cells can be induced in vivo in a manner that models progressive stages of tumorigenesis from nascent neoplasia to the establishment of vascularized tumor masses with an immunosuppressive environment...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29433938/b-cell-lymphoma-immunotherapy-using-tlr9-targeted-oligonucleotide-stat3-inhibitors
#11
Xingli Zhao, Zhuoran Zhang, Dayson Moreira, Yu-Lin Su, Haejung Won, Tomasz Adamus, Zhenyuan Dong, Yong Liang, Hongwei H Yin, Piotr Swiderski, Raju K Pillai, Larry Kwak, Stephen Forman, Marcin Kortylewski
Growing evidence links the aggressiveness of non-Hodgkin's lymphoma, especially the activated B cell-like type diffuse large B cell lymphomas (ABC-DLBCLs) to Toll-like receptor 9 (TLR9)/MyD88 and STAT3 transcription factor signaling. Here, we describe a dual-function molecule consisting of a clinically relevant TLR9 agonist (CpG7909) and a STAT3 inhibitor in the form of a high-affinity decoy oligodeoxynucleotide (dODN). The CpG-STAT3dODN blocked STAT3 DNA binding and activity, thus reducing expression of downstream target genes, such as MYC and BCL2L1, in human and mouse lymphoma cells...
January 17, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29431691/low-dose-methotrexate-prevents-primary-and-secondary-humoral-immune-responses-and-induces-immune-tolerance-to-a-recombinant-immunotoxin
#12
Emily M King, Ronit Mazor, Nicolas Çuburu, Ira Pastan
Recombinant immunotoxins (RITs) are chimeric proteins being developed for cancer treatment. They are composed of an Ab fragment that targets a cancer Ag and a cytotoxic portion of Pseudomonas exotoxin A. They are effective for patients with hematologic malignancies with defective immunity, but their efficacy against solid tumors is limited by anti-drug Ab (ADA) responses in immune-competent patients. Pre-existing Abs or immune memory owing to previous toxin exposure represent additional hurdles because they induce rapid and strong ADA responses...
February 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29430789/intratumoral-delivery-of-interferon-%C3%AE-secreting-mscs-repolarizes-tumor-associated-macrophages-and-suppresses-neuroblastoma-proliferation-in-vivo
#13
Theresa Relation, Tai Yi, Adam J Guess, Krista La Perle, Satoru Otsuru, Suheyla Hasgur, Massimo Dominici, Christopher Breuer, Edwin M Horwitz
Neuroblastoma, the most common extracranial solid tumor in childhood, remains a therapeutic challenge. However, one promising patient treatment strategy is the delivery of anti-tumor therapeutic agents via mesenchymal stromal cell (MSC) therapy. MSCs have been safely utilized to treat genetic bone diseases such as osteogenesis imperfecta, cardiovascular diseases, autoimmune diseases, and cancer. The pro-inflammatory cytokine interferon-gamma (IFNγ) has been shown to decrease tumor proliferation by altering the tumor microenvironment (TME)...
February 12, 2018: Stem Cells
https://www.readbyqxmd.com/read/29428221/the-inflammatory-microenvironment-that-promotes-gastrointestinal-cancer-development-and-invasion
#14
REVIEW
Kanae Echizen, Hiroko Oshima, Mizuho Nakayama, Masanobu Oshima
Accumulating evidence has indicated that the inflammatory response is important for tumor promotion. However, the mechanisms underlying the induction of the inflammatory response in cancer tissues and how it promotes tumorigenesis remain poorly understood. We constructed several mouse models that develop inflammation-associated gastric and intestinal tumors and examined the in vivo mechanisms of tumorigenesis. Of note, the activation of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway and Toll-like receptor (TLR)/MyD88 signaling cooperatively induced the generation of an inflammatory microenvironment, which is required for early-stage tumorigenesis...
February 5, 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29427592/establishment-of-engineered-cell-based-assays-mediating-lag3-and-pd1-immune-suppression-enables-potency-measurement-of-blocking-antibodies-and-assessment-of-signal-transduction
#15
Bhagyashree Bhagwat, Holly Cherwinski, Manjiri Sathe, Wolfgang Seghezzi, Terrill K McClanahan, Rene de Waal Malefyt, Aarron Willingham
LAG3 is an important regulator of T cell homeostasis and studies in mouse tumor models have demonstrated that simultaneously antagonizing LAG3 and PD1 can augment tumor-specific T cell responses and induce tumor rejection. The combined use of LAG3 antagonist antibodies with established anti-PD1 therapies is currently being evaluated in human clinical trials. A functional assay for human LAG3 was developed by co-culture of a Jurkat T-cell lymphoma line overexpressing LAG3 with a Raji B-cell lymphoma line in the presence of staphylococcal enterotoxins...
February 7, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29423114/germline-polymorphism-of-interferon-lambda3-is-clinically-associated-with-progression-of-renal-cell-carcinoma
#16
Akinori Nukui, Yoshiaki Yanai, Toyonori Tsuzuki, Hideyuki Abe, Kyoko Arai, Ken-Ichiro Yoshida, Takao Kamai
Renal cell carcinoma (RCC) is an immunogenic tumor that shows a metabolic shift to aerobic glycolysis. The immune system can have opposing host-protective and tumor-promoting effects, and aerobic glycolysis suppresses antitumor immunity. In addition to immunostimulatory effect, increasing numbers of studies have revealed that interferon (IFN) is also involved in promoting immunosuppression. Since various single nucleotide polymorphisms (SNPs) can influence the outcome of anticancer therapy, we investigated SNPs for IFN-lambda3, a new member of IFN family, in 53 patients with metastatic RCC who underwent cytoreductive nephrectomy...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29422777/imiquimod-inhibits-growth-and-induces-differentiation-of-myeloid-leukemia-cell-lines
#17
Eva Villamón, Javier González-Fernández, Esperanza Such, José Vicente Cervera, Daniel Gozalbo, M Luisa Gil
Background: The antitumoral effects of different Toll-like receptor (TLRs) agonists is mediated by activating immune responses to suppress tumors growth, although TLR ligands may also have a direct effect on tumoral cells. Given that TLR signaling induces hematopoietic cell differentiations this may serve as a novel differentiation therapeutic approach for AML. Methods: We investigated the effects of agonists for the ten human TLRs on the proliferation, apoptosis, cell cycle and differentiation of ten different types of myeloid leukemia cell lines (HL-60, U-937, KG-1, KG-1a, K-562, Kasumi-1, EOL-1, NB4, MOLM-13 and HEL)...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29419408/distinct-pathogenesis-of-pancreatic-cancer-microvesicle-associated-venous-thrombosis-identifies-new-antithrombotic-targets-in-vivo
#18
Konstantin Stark, Irene Schubert, Urjita Joshi, Badr Kilani, Parandis Hoseinpour, Manovriti Thakur, Petra Grünauer, Susanne Pfeiler, Tobias Schmidergall, Sven Stockhausen, Markus Bäumer, Sue Chandraratne, Marie-Luise von Brühl, Michael Lorenz, Raffaele Coletti, Sven Reese, Iina Laitinen, Sonja Maria Wörmann, Hana Algül, Christiane J Bruns, Jerry Ware, Nigel Mackman, Bernd Engelmann, Steffen Massberg
OBJECTIVE: Cancer patients are at high risk of developing deep venous thrombosis (DVT) and venous thromboembolism, a leading cause of mortality in this population. However, it is largely unclear how malignant tumors drive the prothrombotic cascade culminating in DVT. APPROACH AND RESULTS: Here, we addressed the pathophysiology of malignant DVT compared with nonmalignant DVT and focused on the role of tumor microvesicles as potential targets to prevent cancer-associated DVT...
February 1, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29417766/limiting-glioma-development-by-photodynamic-therapy-generated-macrophage-vaccine-and-allo-stimulation-an-in-vivo-histological-study-in-rats
#19
Steen J Madsen, Catherine Christie, Khoi Huynh, Qian Peng, Francisco A Uzal, Tatiana B Krasieva, Henry Hirschberg
Immunotherapy of brain tumors involves the stimulation of an antitumor immune response. This type of therapy can be targeted specifically to tumor cells thus sparing surrounding normal brain. Due to the presence of the blood-brain barrier, the brain is relatively isolated from the systemic circulation and, as such, the initiation of significant immune responses is more limited than other types of cancers. The purpose of this study was to show that the efficacy of tumor primed antigen presenting macrophage (MaF98) vaccines can be increased by: (1) photodynamic therapy (PDT) of the priming tumor cells and (2) intracranial injection of allogeneic glioma cells directly into the tumor site...
February 2018: Journal of Biomedical Optics
https://www.readbyqxmd.com/read/29415817/heterologous-human-rat-her2-specific-exosome-targeted-t-cell-vaccine-stimulates-potent-humoral-and-ctl-responses-leading-to-enhanced-circumvention-of-her2-tolerance-in-double-transgenic-hla-a2-her2-mice
#20
Yufeng Xie, Jie Wu, Aizhang Xu, Shahid Ahmeqd, Amer Sami, Rajni Chibbar, Andrew Freywald, Changyu Zheng, Jim Xiang
DNA vaccines composed of heterologous human HER2 and rat neu sequences induce stronger antibody response and protective antitumor immunity than either HER2 or neu DNA vaccines in transgenic mice. We previously developed HER2-specific exosome-targeted T-cell vaccine HER2-TEXO capable of stimulating HER2-specific CD8+ T-cell responses, but only leading to partial protective immunity in double-transgenic HLA-A2/HER2 mice with self-immune tolerance to HER2. Here, we constructed an adenoviral vector AdVHuRt expressing HuRt fusion protein composed of NH2-HER21-407 (Hu) and COOH-neu408-690 (Rt) fragments, and developed a heterologous human/rat HER2-specific exosome-targeted T-cell vaccine HuRt-TEXO using polyclonal CD4+ T-cells uptaking exosomes released by AdVHuRt-transfected dendritic cells...
February 5, 2018: Vaccine
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