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https://www.readbyqxmd.com/read/30523022/molecular-subtype-not-immune-response-drives-outcomes-in-endometrial-carcinoma
#1
Aline Talhouk, Heather Derocher, Pascal Schmidt, Samuel Leung, Katy Milne, Blake Gilks, Michael S Anglesio, Brad H Nelson, Jessica N McAlpine
PURPOSE: Tumors with high mutation load are thought to engender stronger immune responses which in turn promote prolonged patient survival. To investigate this, we assessed tumor-infiltrating lymphocytes (TIL) and immunosuppressive factors across the four molecular subtypes of endometrial cancer (EC), which have characteristic mutation rates ranging from low to ultra-high. EXPERIMENTAL DESIGN: 460 ECs were stratified by ProMisE (Proactive Molecular Risk Classifier in Endometrial cancer) into four molecular subtypes: mismatch repair-deficient (MMRd), POLE mutant (POLE), p53 abnormal (p53abn), and p53 wildtype (p53wt)...
December 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30498709/cytokinome-of-adult-derived-human-liver-stem-progenitor-cells-immunological-and-inflammatory-features
#2
Mehdi Najar, Emerence Crompot, Gordana Raicevic, Etienne M Sokal, Mustapha Najimi, Laurence Lagneaux
Background: Being non-immunogenic and capable of achieving major metabolic liver functions, adult-derived human liver stem/progenitor cells (ADHLSCs) are of special interest in the field of liver cell therapy. The cytokine repertoire of engrafted cells may have critical impacts on the immune response balance, particularly during cell transplantation. Methods: In this work, we analyzed the cytokinome of ADHLSCs during hepatogenic differentiation (HD) following stimulation with a mixture of inflammatory cytokines (I) in vitro and compared it to that of mature hepatocytes...
October 2018: Hepatobiliary Surgery and Nutrition
https://www.readbyqxmd.com/read/30481959/breast-cancer-chemo-immunotherapy-through-liposomal-delivery-of-an-immunogenic-cell-death-stimulus-plus-interference-in-the-ido-1-pathway
#3
Jianqin Lu, Xiangsheng Liu, Yu-Pei Liao, Xiang Wang, Ayman Ahmed, Wen Jiang, Ying Ji, Huan Meng, Andre E Nel
Immunotherapy provides the best approach to reduce the high mortality of metastatic breast cancer (BC). We demonstrate a chemo-immunotherapy approach, which utilizes a liposomal carrier to simultaneously trigger immunogenic cell death (ICD) as well as interfere in the regionally overexpressed immunosuppressive effect of indoleamine 2,3-dioxygenase (IDO-1) at the BC tumor site. The liposome was constructed by self-assembly of a phospholipid-conjugated prodrug, indoximod (IND), which inhibits the IDO-1 pathway, followed by the remote loading of the ICD-inducing chemo drug, doxorubicin (DOX)...
November 27, 2018: ACS Nano
https://www.readbyqxmd.com/read/30468988/okn-007-increases-temozolomide-tmz-sensitivity-and-suppresses-tmz-resistant-glioblastoma-gbm-tumor-growth
#4
Rheal A Towner, Nataliya Smith, Debra Saunders, Chase A Brown, Xue Cai, Jadith Ziegler, Samantha Mallory, Mikhail G Dozmorov, Patricia Coutinho De Souza, Graham Wiley, Kyeongsoon Kim, Shinwook Kang, Doo-Sik Kong, Young-Tae Kim, Kar-Ming Fung, Jonathan D Wren, James Battiste
Treatment of glioblastoma (GBM) remains a challenge using conventional chemotherapy, such as temozolomide (TMZ), and is often ineffective as a result of drug resistance. We have assessed a novel nitrone-based agent, OKN-007, and found it to be effective in decreasing tumor volumes and increasing survival in orthotopic GBM xenografts by decreasing cell proliferation and angiogenesis and increasing apoptosis. In this study, we assessed combining OKN-007 with TMZ in vivo in a human G55 GBM orthotopic xenograft model and in vitro in TMZ-resistant and TMZ-sensitive human GBM cell lines...
November 20, 2018: Translational Oncology
https://www.readbyqxmd.com/read/30448912/assessment-of-tils-ido-1-and-pd-l1-in-resected-non-small-cell-lung-cancer-an-immunohistochemical-study-with-clinicopathological-and-prognostic-implications
#5
Martina Mandarano, Guido Bellezza, Maria Laura Belladonna, Benoit J Van den Eynde, Rita Chiari, Jacopo Vannucci, Giada Mondanelli, Vienna Ludovini, Ivana Ferri, Fortunato Bianconi, Rachele Del Sordo, Lucio Cagini, Elisa Albini, Giulio Metro, Francesco Puma, Angelo Sidoni
Several cancers, especially non-small cell lung cancer (NSCLC), are able to escape the immunosurveillance of tumor-infiltrating lymphocytes (TILs); among the molecules involved, the indoleamine 2,3-dioxygenase 1 (IDO-1) and the programmed cell death ligand-1 (PD-L1) play a crucial role. These aspects are of great interest in the current immunotherapeutic era, therefore the current study analyses the TILs, IDO-1, and PD-L1 interactions and their correlations with clinicopathological parameters and prognosis in NSCLC...
November 17, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/30426184/ameliorative-effect-of-fisetin-against-lipopolysaccharide-and-restraint-stress-induced-behavioral-deficits-via-modulation-of-nf-%C3%AE%C2%BAb-and-ido-1
#6
Priyansha Choubey, Mohit Kwatra, Surya Narayan Pandey, Dinesh Kumar, Durgesh Kumar Dwivedi, Prabha Rajput, Abhishek Mishra, Mangala Lahkar, Ashok Jangra
BACKGROUND: Fisetin, a plant active polyphenol, is well known for its antioxidant and free radical scavenging activities. The present study was designed to explore the detailed molecular mechanism underlying its neuroprotective effects. METHODS: The young male mice were either administered a single dose of lipopolysaccharide (0.83 mg/kg) or subjected to restraint stress (6 h per day for 28 days) to induce behavioral deficits in different groups. Fisetin (15 mg/kg) was orally administered for the last 14 days of the study...
November 14, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/30289282/immunoregulatory-effects-of-indole-3-carbinol-on-monocyte-derived-macrophages-in-systemic-lupus-erythematosus-a-crucial-role-for-aryl-hydrocarbon-receptor
#7
Saeed Mohammadi, Ali Memarian, Sima Sedighi, Nasser Behnampour, Yaghoub Yazdani
Macrophages are versatile phagocytic cells in immune system with immunoregulatory functions. However, the removal of apoptotic cells by macrophages is disturbed in systemic lupus erythematosus (SLE). Aryl hydrocarbon receptor (AhR) is a ligand-activated cytoplasmic receptor and transcription factor with diverse effects on immune response. Indole-3-carbinol (I3C) is an AhR agonist which has been implicated as a beneficial factor in regulating inflammation and cytokine expression in murine models of SLE. However, the molecular mechanisms are not thoroughly studied...
October 5, 2018: Autoimmunity
https://www.readbyqxmd.com/read/30243842/palmatine-ameliorated-murine-colitis-by-suppressing-tryptophan-metabolism-and-regulating-gut-microbiota
#8
Xiao-Jun Zhang, Zhong-Wen Yuan, Chang Qu, Xiu-Ting Yu, Tao Huang, Ping Vicky Chen, Zi-Ren Su, Yao-Xing Dou, Jia-Zhen Wu, Hui-Fang Zeng, Ying Xie, Jian-Nan Chen
Inflammatory bowel disease (IBD), majorly include Crohn's disease (CD) and ulcerative colitis (UC), is chronic and relapsing inflammatory disorders of the gastrointestinal tract, which treatment options remain limited. Here we examined the therapeutic effects of an isoquinoline alkaloid, Palmatine (Pal), on mice experimental colitis induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Colitis was induced in BALB/c mice by administering 3% DSS in drinking water for 7 days. Pal (50 and 100 mg kg-1 ) and the positive drug Sulfasalazine (SASP, 200 mg kg-1 ) were orally administered for 7 days...
September 19, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30128151/tryptophan-and-arginine-catabolic-enzymes-and-regulatory-cytokines-in-clinically-isolated-syndrome-and-multiple-sclerosis
#9
Lilian Cha, Anderson P Jones, Stephanie Trend, Scott N Byrne, Marzena J Fabis-Pedrini, William M Carroll, Robyn M Lucas, Judith M Cole, David R Booth, Allan G Kermode, Prue H Hart
Objectives: Clinically isolated syndrome (CIS) is the earliest clinical episode in multiple sclerosis (MS). A study of circulating cells from patients with CIS may help us understand the transition to, and processes associated with, the development of MS. Methods: As immune cell activity can be determined by flux through metabolic pathways, the mRNA expression of l-tryptophan- and l-arginine-catabolising enzymes, indoleamine 2,3-dioxygenase (IDO) 1 and IDO2 and arginase (ARG) 1 and ARG2, respectively, was compared between peripheral blood mononuclear cells (PBMCs) from healthy controls, and patients with CIS and definite MS...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/30063262/binary-cooperative-prodrug-nanoparticles-improve-immunotherapy-by-synergistically-modulating-immune-tumor-microenvironment
#10
Bing Feng, Fangyuan Zhou, Bo Hou, Dangge Wang, Tingting Wang, Yuanlei Fu, Yuting Ma, Haijun Yu, Yaping Li
Checkpoint blockade immunotherapy is promising for clinical treatment of various malignant tumors. However, checkpoint blockade immunotherapy suffers from a low response rate due to insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment (ITM). In this study, a tumor-microenvironment-activatable binary cooperative prodrug nanoparticle (BCPN) is rationally designed to improve immunotherapy by synergistically modulating the immune tumor microenvironment. BCPN is purely constructed from a tumor acidity and reduction dual-responsive oxaliplatin (OXA) prodrug for triggering immunogenic cell death (ICD) and eliciting antitumor immunity, and a reduction-activatable homodimer of NLG919 for inactivating indoleamine 2,3-dioxygenase 1, which is a key regulator for ITM...
July 31, 2018: Advanced Materials
https://www.readbyqxmd.com/read/30054585/resolution-of-inflammation-induced-depression-requires-t-lymphocytes-and-endogenous-brain-interleukin-10-signaling
#11
Geoffroy Laumet, Jules Daniel Edralin, Angie Chi-An Chiang, Robert Dantzer, Cobi J Heijnen, Annemieke Kavelaars
In humans, depression is often associated with low-grade inflammation, activation of the tryptophan/kynurenine pathway, and mild lymphopenia. Preclinical research confirms that inflammation induces depression-like behavior through activation of the tryptophan/kynurenine pathway. However, the mechanisms governing recovery from depression are unknown. Understanding the pathways leading to resolution of depression will likely lead to identification of novel targets for treatment. We investigated the contribution of T lymphocytes to the resolution of lipopolysaccharide-induced depression-like behavior...
December 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/30048487/cytokine-secretion-responsiveness-of-lymphomonocytes-following-cortisol-cell-exposure-sex-differences
#12
Eleonora Da Pozzo, Chiara Giacomelli, Chiara Cavallini, Claudia Martini
The stress hormone cortisol has been recognized as a coordinator of immune response. However, its different ability to modulate the release of inflammatory mediators in males and females has not been clarified yet. Indeed, the dissection of cortisol specific actions may be difficult due to the complex hormonal and physio-pathological individual status. Herein, the release of inflammatory mediators following increasing cortisol concentrations was investigated in an in vitro model of primary human male and female lymphomonocytes...
2018: PloS One
https://www.readbyqxmd.com/read/30040142/the-pd-l1-and-il6-mediated-dampening-of-the-il27-stat1-anticancer-responses-are-prevented-by-%C3%AE-pd-l1-or-%C3%AE-il6-antibodies
#13
Catherine Rolvering, Andreas D Zimmer, Aurélien Ginolhac, Christiane Margue, Mélanie Kirchmeyer, Florence Servais, Heike M Hermanns, Sabine Hergovits, Petr V Nazarov, Nathalie Nicot, Stephanie Kreis, Serge Haan, Iris Behrmann, Claude Haan
Interleukin-27 (IL27) is a type-I cytokine of the IL6/IL12 family and is predominantly secreted by activated macrophages and dendritic cells. We show that IL27 induces STAT factor phosphorylation in cancerous cell lines of different tissue origin. IL27 leads to STAT1 phosphorylation and recapitulates an IFN-γ-like response in the microarray analyses, with up-regulation of genes involved in antiviral defense, antigen presentation, and immune suppression. Like IFN-γ, IL27 leads to an up-regulation of TAP2 and MHC-I proteins, which mediate increased tumor immune clearance...
July 24, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/30021908/quantitative-spatial-profiling-of-pd-1-pd-l1-interaction-and-hla-dr-ido-1-predicts-improved-outcomes-of-anti-pd-1-therapies-in-metastatic-melanoma
#14
Douglas B Johnson, Jennifer Bordeaux, Ju Young Kim, Christine Vaupel, David L Rimm, Thai H Ho, Richard W Joseph, Adil I Daud, Robert M Conry, Elizabeth M Gaughan, Leonel F Hernandez-Aya, Anastasios Dimou, Pauline Funchain, James Smithy, John S Witte, Svetlana B McKee, Jennifer Ko, John M Wrangle, Bashar Dabbas, Shabnam Tangri, Jelveh Lameh, Jeffrey Hall, Joseph Markowitz, Justin M Balko, Naveen Dakappagari
Purpose: PD-1/L1 axis-directed therapies produce clinical responses in a subset of patients; therefore, biomarkers of response are needed. We hypothesized that quantifying key immunosuppression mechanisms within the tumor microenvironment by multiparameter algorithms would identify strong predictors of anti-PD-1 response. Experimental Design: Pretreatment tumor biopsies from 166 patients treated with anti-PD-1 across 10 academic cancer centers were fluorescently stained with multiple markers in discovery ( n = 24) and validation ( n = 142) cohorts...
November 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29956749/modulation-of-the-tumor-microenvironment-by-intratumoral-administration-of-imo-2125-a-novel-tlr9-agonist-for-cancer-immunotherapy
#15
Daqing Wang, Wayne Jiang, Fugang Zhu, Xianzhi Mao, Sudhir Agrawal
The objective of cancer immunotherapy is to prime the host's immune system to recognize and attack malignant tumor cells. IMO‑2125, a Toll‑like receptor 9 (TLR9) agonist, exhibited potent antitumor effects in the murine syngeneic A20 lymphoma and the CT26 colon carcinoma models. IMO‑2125 exhibited superior A20 antitumor activity when injected intratumorally (i.t.) compared with equivalent subcutaneous doses. In mice bearing dual CT26 grafts, the i.t. injection of right flank tumors elicited infiltration of cluster of differentiation (CD)3+ T lymphocytes into tumors, resulting in the regression of injected and uninjected left flank tumors...
September 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29901571/indoleamine-2-3-dioxygenase-in-non-small-cell-lung-cancer-a-targetable-mechanism-of-immune-resistance-frequently-coexpressed-with-pd-l1
#16
Ashley Volaric, Ryan Gentzler, Richard Hall, James H Mehaffey, Edward B Stelow, Timothy N Bullock, Linda W Martin, Anne M Mills
The immune regulatory enzyme indoleamine-2,3-dioxygenase (IDO-1) suppresses T cell responses and may reduce efficacy of therapies targeting immune checkpoints such as programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1). Early phase clinical trials combining IDO-1 and PD-1/PD-L1 inhibitors have shown some promise in non-small cell lung cancers (NSCLCs). However, the coexpression of IDO-1 and PD-L1 has not been thoroughly investigated, and the potential for IDO-1 immunohistochemical expression as a therapeutic biomarker is unknown...
September 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29734055/kynurenine-pathway-metabolic-balance-influences-microglia-activity-targeting-kynurenine-monooxygenase-to-dampen-neuroinflammation
#17
Allison M Garrison, Jennifer M Parrott, Arnulfo Tuñon, Jennifer Delgado, Laney Redus, Jason C O'Connor
Chronic stress or inflammation increases tryptophan metabolism along the kynurenine pathway (KP), and the generation of neuroactive kynurenine metabolites contributes to subsequent depressive-like behaviors. Microglia regulate KP balance by preferentially producing oxidative metabolites, including quinolinic acid. Research has focused on the interplay between cytokines and HPA axis-derived corticosteroids in regulating microglial activity and effects of KP metabolites directly on neurons; however, the potential role that KP metabolites have directly on microglial activity is unknown...
August 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29667084/investigation-of-the-aryl-hydrocarbon-receptor-and-the-intrinsic-tumoral-component-of-the-kynurenine-pathway-of-tryptophan-metabolism-in-primary-brain-tumors
#18
Anthony R Guastella, Sharon K Michelhaugh, Neil V Klinger, Hassan A Fadel, Sam Kiousis, Rouba Ali-Fehmi, William J Kupsky, Csaba Juhász, Sandeep Mittal
INTRODUCTION: There is mounting evidence supporting the role of tryptophan metabolism via the kynurenine pathway (KP) in the pathogenesis of primary brain tumors. Under normal physiological conditions, the KP is the major catabolic pathway for the essential amino acid tryptophan. However, in cancer cells, the KP becomes dysregulated, depletes local tryptophan, and contributes to an immunosuppressive tumor microenvironment. METHODS: We examined the protein expression levels (in 73 gliomas and 48 meningiomas) of the KP rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, and tryptophan 2,3-dioxygenase (TDO2), as well as, the aryl hydrocarbon receptor (AhR), a carcinogenic transcription factor activated by KP metabolites...
September 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29576845/immunomodulatory-effects-of-diterpene-quinone-derivatives-from-the-roots-of-horminum-pyrenaicum-in-human-pbmc
#19
K Becker, S Schwaiger, B Waltenberger, D Fuchs, C K Pezzei, H Schennach, H Stuppner, J M Gostner
Several phytochemicals were shown to interfere with redox biology in the human system. Moreover, redox biochemistry is crucially involved in the orchestration of immunological cascades. When screening for immunomodulatory compounds, the two interferon gamma- (IFN- γ -) dependent immunometabolic pathways of tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) and neopterin formation by GTP-cyclohydrolase 1 (GTP-CH-I) represent prominent targets, as IFN- γ -related signaling is strongly sensitive to oxidative triggers...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29548707/inducible-indoleamine-2-3-dioxygenase-1-and-programmed-death-ligand-1-expression-as-the-potency-marker-for-mesenchymal-stromal-cells
#20
Qingdong Guan, Yun Li, Tanner Shpiruk, Swaroop Bhagwat, Donna A Wall
AIM: Establishment of a potency assay in the manufacturing of clinical-grade mesenchymal stromal cells (MSCs) has been a challenge due to issues of relevance to function, timeline and variability of responder cells. In this study, we attempted to develop a potency assay for MSCs. METHODS: Clinical-grade bone marrow-derived MSCs were manufactured. The phenotype and immunosuppressive functions of the MSCs were evaluated based on the International Society for Cellular Therapy guidelines...
May 2018: Cytotherapy
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