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https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#1
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29764164/immunoregulatory-antigens-novel-targets-for-cancer-immunotherapy
#2
Ayako Wakatsuki Pedersen, Katharina L Kopp, Mads Hald Andersen, Mai-Britt Zocca
Historically, the development of cancer vaccines has focused on the central role of tumor antigens in eliciting tumor-specific immune responses, with limited success. Recent advances with checkpoint blockade approaches have brought about a renewed appreciation of the importance of targeting immune suppression in cancer patients. Here we discuss a novel approach to cancer immunotherapy, namely to target recently described T cells that uniquely control cells with immune suppressive functions. Accumulating evidence support the existence of self-reactive T cells that are specific to antigens derived from immunoregulatory proteins ("immunoregulatory antigens"), such as indoleamine 2,3-dioxygenase (IDO) and PD-L1...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29760736/comparison-of-immunological-characteristics-of-mesenchymal-stem-cells-from-the-periodontal-ligament-umbilical-cord-and-adipose-tissue
#3
Jin-Hee Kim, Chris H Jo, Hang-Rae Kim, Young-Il Hwang
Mesenchymal stem cells (MSCs) are of therapeutic importance in the fields of regenerative medicine and immunological diseases. Accordingly, studies evaluating MSCs for clinical applications are increasing. In this study, we characterized MSCs from the periodontal ligament, umbilical cord (UC-MSCs), and adipose tissue, which were relatively easy to obtain with limited ethical concerns regarding their acquisition, and compared their immunological characteristics. Among MSCs isolated from the three different tissues, UC-MSCs grew the fastest in vitro ...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29760410/motivational-changes-that-develop-in-a-mouse-model-of-inflammation-induced-depression-are-independent-of-indoleamine-2-3-dioxygenase
#4
Elisabeth G Vichaya, Geoffroy Laumet, Diana L Christian, Aaron J Grossberg, Darlene J Estrada, Cobi J Heijnen, Annemieke Kavelaars, Robert Dantzer
Despite years of research, our understanding of the mechanisms by which inflammation induces depression is still limited. As clinical data points to a strong association between depression and motivational alterations, we sought to (1) characterize the motivational changes that are associated with inflammation in mice, and (2) determine if they depend on inflammation-induced activation of indoleamine 2,3 dioxygenase-1 (IDO1). Lipopolysaccharide (LPS)-treated or spared nerve injured (SNI) wild type (WT) and Ido1 -/- mice underwent behavioral tests of antidepressant activity (e...
April 27, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29759005/ido-expressing-fibroblasts-suppress-the-development-of-imiquimod-induced-psoriasis-like-dermatitis
#5
Sanam Salimi Elizei, Mohammadreza Pakyari, Mehraneh Ghoreishi, Ruhangiz Kilani, Sanaz Mahmoudi, Aziz Ghahary
Psoriasis is a chronic skin condition whose pathogenesis is reported to be due to the activation of the interleukin-23/interleukin-17 (IL-23/IL-17) pathway. Here, we report that indoleamine 2,3-dioxygenase (IDO)-expressing fibroblasts reduce the activity of this pathway in activated immune cells. The findings showed that intralesional injection of IDO-expressing fibroblasts in imiquimod-induced psoriasis-like dermatitis on the back and ear (Pso. ear group) in mice significantly improves the clinical lesional appearance by reducing the number of skin-infiltrated IL-17+ CD4+ T cells (1...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29754847/feasibility-of-classification-of-triple-negative-breast-cancer-by-immunohistochemical-surrogate-markers
#6
Sewha Kim, Byung-In Moon, Woosung Lim, Sanghui Park, Min Sun Cho, Sun Hee Sung
INTRODUCTION: Recently, Burstein et al identified 4 stable molecular subtypes of triple negative breast cancer (TNBC) by mRNA profiling: luminal androgen receptor (LAR), mesenchymal (MES), basal-like immune-activated (BLIA), and basal-like immune-suppressive (BLIS) types. The purpose of this study was to assess the feasibility of immunohistochemistry (IHC) surrogate panel in classifying the TNBC molecular subtypes using a large cohort of TNBC retrieved from a single institution. MATERIALS AND METHODS: IHC for androgen receptor [AR], claudin-3, E-cadherin, cytokeratin 5/6 [CK5/6], epidermal growth factor receptor [EGFR], indoleamine 2,3-dioxygenase 1 [IDO1], and Forkhead box C1 [FOXC1] were performed using the tissue microarray constructed from 200 TNBC samples...
March 23, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29752722/a-new-cancer-immunotherapy-via-simultaneous-dc-mobilization-and-dc-targeted-ido-gene-silencing-using-an-immune-stimulatory-nanosystem
#7
Yujuan Zhang, Jiamin Fu, Yanmei Shi, Shanshan Peng, Ying Cai, Xuelin Zhan, Na Song, Yanling Liu, Zhigang Wang, Yanrong Yu, Yifan Wang, Qiaofa Shi, Yingyuan Fu, Keng Yuan, Nanjin Zhou, Rakesh Joshi, Thomas E Ichim, Weiping Min
The activity of negative immune regulatory molecules, such as indoleamine 2,3-oxygenase (IDO), significantly attenuates DC (Dendritic cells)-mediated immunotherapy. We have previously reported that knockdown of IDO using siRNA can reinstall anti-tumor immunity. However, a DC-targeted siRNA delivery system for in vivo mobilized DCs remains to be developed, while gene silencing in mobilized DCs for cancer immunotherapy has never been explored. In this study, we developed a novel DC-targeted siRNA delivery system, man-GNR-siIDO, using as a nanocarrier of siRNA specific for IDO (siIDO) and mannose (man) as a guide molecule for targeting DCs...
May 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29752140/feiji-recipe-inhibits-the-growth-of-lung-cancer-by-modulating-t-cell-immunity-through-indoleamine-2-3-dioxygenase-pathway-in-an-orthotopic-implantation-model
#8
Bin Luo, Zu-Jun Que, Zhi-Yi Zhou, Qing Wang, Chang-Sheng Dong, Yi Jiang, Bing Hu, Hui Shi, Yu Jin, Jian-Wen Liu, He-Gen Li, Lin Wang, Jian-Hui Tian
OBJECTIVE: Escape from the body's immune response is a basic characteristic of lung cancer, and indoleamine-2,3-dioxygenase (IDO) plays a key role in mediating immune escape of non-small-cell lung cancer, which leads to recurrence and metastasis. Feiji Recipe, a compound Chinese herbal medicine, has the effect of stabilizing lesions and prolonging survival in patients with lung cancer. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of Feiji Recipe...
April 22, 2018: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29746927/indoleamine-2-3-dioxygenase-1-inhibition-targets-anti-pd1-resistant-lung-tumors-by-blocking-myeloid-derived-suppressor-cells
#9
Ailin Li, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Taylor R Cushman, Mauricio S Caetano, Xiaohong Wang, David R Valdecanas, Sharareh Niknam, Ahmed I Younes, Guang Li, Wendy A Woodward, Maria Angelica Cortez, James W Welsh
Indoleamine 2,3-dioxygenase 1 (IDO1), involved in the catabolism of tryptophan (Trp) to kynurenine (Kyn) is an important regulator of tumor-mediated immunosuppression implicated in resistance to anti-PD1 immunotherapy. We investigated the role of IDO1 in an anti-PD1-resistant lung cancer model (344SQ_R) compared to the parental 344SQ tumors (344SQ_P). IDO1 was overexpressed in tumor-infiltrating leukocytes, and plasma Kyn levels were increased, in 344SQ_R vs. 344SQ_P. The IDO1 inhibitor INCB023843 retarded tumor growth and reduced lung metastases in 344SQ_R...
May 7, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29746559/comparative-genotypic-and-phenotypic-analysis-of-human-peripheral-blood-monocytes-and-surrogate-monocyte-like-cell-lines-commonly-used-in-metabolic-disease-research
#10
Darren M Riddy, Emily Goy, Philippe Delerive, Roger J Summers, Patrick M Sexton, Christopher J Langmead
Monocyte-like cell lines (MCLCs), including THP-1, HL-60 and U-937 cells, are used routinely as surrogates for isolated human peripheral blood mononuclear cells (PBMCs). To systematically evaluate these immortalised cells and PBMCs as model systems to study inflammation relevant to the pathogenesis of type II diabetes and immuno-metabolism, we compared mRNA expression of inflammation-relevant genes, cell surface expression of cluster of differentiation (CD) markers, and chemotactic responses to inflammatory stimuli...
2018: PloS One
https://www.readbyqxmd.com/read/29745343/indazoles-derivatives-promising-anti-tumor-agents
#11
Yichao Wan, Shengzhuo He, Wei Li, Zilong Tang
Currently, cancer continues being a dramatically increasing and serious threat to public health. Although many anti-tumor agents have been developed in recent years, the survival rate of patients is not satisfactory. The poor prognosis of cancer patients is closely related to the occurrence of drug resistance. Therefore, it is urgent to develop new anti-tumor agents to make up for the deficiency. Indazoles is an important class of heterocyclic compounds possessing a variety of biological activities, such as anti-tumor, anti-bacterial, anti-inflammatory, anti-depressant and anti-hypertensive...
May 9, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29743880/-trypanosoma-cruzi-exploits-wnt-signaling-pathway-to-promote-its-intracellular-replication-in-macrophages
#12
Ximena Volpini, Laura F Ambrosio, Laura Fozzatti, Constanza Insfran, Cinthia C Stempin, Laura Cervi, Claudia Cristina Motran
During the acute phase of Trypanosoma cruzi infection, macrophages can act as host cells for the parasites as well as effector cells in the early anti-parasitic immune response. Thus, the targeting of specific signaling pathways could modulate macrophages response to restrict parasite replication and instruct an appropriate adaptive response. Recently, it has become evident that Wnt signaling has immunomodulatory functions during inflammation and infection. Here, we tested the hypothesis that during T. cruzi infection, the activation of Wnt signaling pathway in macrophages plays a role in modulating the inflammatory/tolerogenic response and therefore regulating the control of parasite replication...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29742432/il-9-and-mast-cells-are-key-players-of-candida-albicans-commensalism-and-pathogenesis-in-the-gut
#13
Giorgia Renga, Silvia Moretti, Vasilis Oikonomou, Monica Borghi, Teresa Zelante, Giuseppe Paolicelli, Claudio Costantini, Marco De Zuani, Valeria Rachela Villella, Valeria Raia, Rachele Del Sordo, Andrea Bartoli, Monia Baldoni, Jean-Christophe Renauld, Angelo Sidoni, Enrico Garaci, Luigi Maiuri, Carlo Pucillo, Luigina Romani
Candida albicans is implicated in intestinal diseases. Identifying host signatures that discriminate between the pathogenic versus commensal nature of this human commensal is clinically relevant. In the present study, we identify IL-9 and mast cells (MCs) as key players of Candida commensalism and pathogenicity. By inducing TGF-β in stromal MCs, IL-9 pivotally contributes to mucosal immune tolerance via the indoleamine 2,3-dioxygenase enzyme. However, Candida-driven IL-9 and mucosal MCs also contribute to barrier function loss, dissemination, and inflammation in experimental leaky gut models and are upregulated in patients with celiac disease...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29740779/forced-expression-of-cd200-improves-the-differentiation-capability-and-immunoregulatory-functions-of-mesenchymal-stromal-cells
#14
Hye Joung Kim, Kyoung-Woon Kim, Yong-Rim Kwon, Bo-Mi Kim, Yoo-Jin Kim
OBJECTIVE: In order to identify specific mesenchymal stromal cell (MSC) populations with enhanced therapeutic efficacy, we evaluated the functional changes associated with the stable expression of CD200, which is associated with immune regulatory function and osteogenic differentiation, in human bone marrow-derived MSCs (CD200/MSCs). RESULTS: We detected significantly greater osteogenesis and chondrogenesis in CD200/MSCs than in mock-transfected MSCs. In addition, the immune regulatory function of MSCs in mixed lymphocyte reactions was enhanced by CD200 gene transfection...
May 9, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29734055/kynurenine-pathway-metabolic-balance-influences-microglia-activity-targeting-kynurenine-monooxygenase-to-dampen-neuroinflammation
#15
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...
April 22, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29730433/the-tolerogenic-peptide-hcdr1-immunomodulates-cytokine-and-regulatory-molecule-gene-expression-in-blood-mononuclear-cells-of-primary-sjogren-s-syndrome-patients
#16
Zev Sthoeger, Amir Sharabi, Ilan Asher, Heidy Zinger, Rafael Segal, Gene Shearer, Ori Elkayam, Edna Mozes
Primary Sjogren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands. We investigated whether the tolerogenic peptide, hCDR1, that ameliorates lupus manifestations would have beneficial effects on pSS as well. The in vitro effects of hCDR1 on gene expression of pro-inflammatory cytokines and regulatory molecules were tested in peripheral blood mononuclear cells (PBMC) of 16 pSS patients. hCDR1, but not a control peptide, significantly reduced gene expression of IL-1β, TNF-α, MX-1 and BlyS and up-regulated immunosuppressive (TGF-β, FOXP3) molecules in PBMC of pSS patients...
May 3, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29725904/chronic-mild-stress-alters-kynurenine-pathways-changing-the-glutamate-neurotransmission-in-frontal-cortex-of-rats
#17
David Martín-Hernández, Hiram Tendilla-Beltrán, José L M Madrigal, Borja García-Bueno, Juan C Leza, Javier R Caso
Immune stimulation might be involved in the pathophysiology of major depressive disorder (MDD). This stimulation induces indoleamine 2,3-dioxygenase (IDO), an enzyme that reduces the tryptophan bioavailability to synthesize serotonin. IDO products, kynurenine metabolites, exert neurotoxic/neuroprotective actions through glutamate receptors. Thus, we study elements of these pathways linked to kynurenine metabolite activity examining whether antidepressants (ADs) can modulate them. Male Wistar rats were exposed to chronic mild stress (CMS), and some of them were treated with ADs...
May 3, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29724044/mechanisms-of-intrinsic-tumor-resistance-to-immunotherapy
#18
REVIEW
John Rieth, Subbaya Subramanian
An increased understanding of the interactions between the immune system and tumors has opened the door to immunotherapy for cancer patients. Despite some success with checkpoint inhibitors including ipilimumab, pembrolizumab, and nivolumab, most cancer patients remain unresponsive to such immunotherapy, likely due to intrinsic tumor resistance. The mechanisms most likely involve reducing the quantity and/or quality of antitumor lymphocytes, which ultimately are driven by any number of developments: tumor mutations and adaptations, reduced neoantigen generation or expression, indoleamine 2,3-dioxygenase (IDO) overexpression, loss of phosphatase and tensin homologue (PTEN) expression, and overexpression of the Wnt⁻β-catenin pathway...
May 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29722898/lw106-a-novel-inhibitor-of-ido1-suppresses-tumor-progression-by-limiting-stroma-immune-crosstalk-and-cancer-stem-cell-enrichment-in-the-tumor-microenvironment
#19
Rong Fu, Yi-Wei Zhang, Hong-Mei Li, Wen-Cong Lv, Li Zhao, Qing-Long Guo, Tao Lu, Stephen J Weiss, Zhi-Yu Li, Zhao-Qiu Wu
BACKGROUND AND PURPOSE: Indoleamine 2,3-dioxygenase 1 (IDO1) is emerging as an important new therapeutic target for treatment of malignant tumors characterized by dysregulated tryptophan metabolism. However, the antitumor efficacy of existing small-molecule inhibitors of IDO1 is still unsatisfactory and the underlying mechanism remains largely undefined. Hence, we discovered a novel potent small-molecule inhibitor of IDO1, LW106, and studied its antitumor effects and the underlying mechanisms in two Tumor models...
May 3, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29719533/high-indoleamine-2-3-dioxygenase-is-correlated-with-microvessel-density-and-worse-prognosis-in-breast-cancer
#20
Lijuan Wei, Shanshan Zhu, Menghui Li, Fangxuan Li, Feng Wei, Juntian Liu, Xiubao Ren
Indoleamine 2,3-dioxygenase (IDO), which catalyzes the breakdown of the essential amino acid tryptophan into kynurenine, is understood to have a key role in cancer immunotherapy. IDO has also received more attention because of its non-immune functions including regulating angiogenesis. The purpose of this study was to investigate the effects of IDO on microvessel density (MVD), and to explore its prognostic role in breast cancer. We showed IDO expression was positively correlated with MVD labeled by CD105 (MVD-CD105) rather than MVD labeled by CD31 (MVD-CD31) in breast cancer specimens...
2018: Frontiers in Immunology
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