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Cancer and IDO

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https://www.readbyqxmd.com/read/29163470/indoleamine-2-3-dioxygenase-and-tolerance-where-are-we-now
#1
REVIEW
Andrew L Mellor, Henrique Lemos, Lei Huang
Cells expressing IDO suppress innate and adaptive immunity to promote tolerance by catabolizing the amino acid tryptophan (Trp) and other indole compounds. Interferon type I (IFN-I) and type II (IFN-II) produced at sites of inflammation or by activated immune cells are potent IDO inducers because mammalian IDO genes contain IFN response elements. Elevated IDO expression by dendritic cells (DCs) is of particular significance because IDO activity converts mature DCs into tolerogenic APCs that suppress effector T cells (Teff) and promote regulatory T cells (Tregs), thereby promoting tolerance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29133258/when-should-patients-undergo-genetic-testing-for-hereditary-colon-cancer-syndromes
#2
Gregory Idos, Samir Gupta
No abstract text is available yet for this article.
November 10, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29128855/selective-inhibition-of-ido1-d-1-methyl-tryptophan-d-1mt-effectively-increased-epcam-cd3-bispecific-bite-antibody-mt110-efficacy-against-ido1-hi-breast-cancer-via-enhancing-immune-cells-activity
#3
Ri Hong, Yuhai Zhou, Xiujuan Tian, Lijuan Wang, Xiaoyun Wu
MuS110 and MT110 are BiTE antibodies bispecific for CD3 and EpCAM, which is the most frequently and highly expressed tumor-associated antigen on breast cancer. And pronounced expression of IDO1 has also been reported in breast cancer. Our study aimed to investigate whether IDO1 inhibitor D-1MT combing with MuS110/MT110 had synergistic antitumor effects on IDO expressing EpCAM-positive breast cancer cells in vitro and in vivo. Data suggested that the expression of IDO1 on Epcam-positive breast cancer 4T1 and MCF-7 decreased MuS110/MT110 antitumor efficacy by the suppression of T cells activation in vitro...
November 9, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29118088/ido-immune-status-after-chemoradiation-may-predict-survival-in-lung-cancer-patients
#4
Weili Wang, Lei Huang, Jian-Yue Jin, Shruti Jolly, Yong Zang, Huanmei Wu, Li Yan, Wenhu Pi, Lang Li, Andrew L Mellor, Feng-Ming Spring Kong
Host immunity influences the impact of radiotherapy (RT) in cancer but mechanistic connections remain obscure. In this study, we investigated the relationship of indoleamine 2,3-dioxygenase (IDO) systemic activity on clinical outcomes in RT-treated non-small cell lung cancer (NSCLC). IDO-mediated production of kynurenine and the kynurenine:tryptophan ratio in patient blood serum were determined for stage III NSCLC patients at times before, during and after RT administration and then correlated to overall survival (OS), progression-free survival and disease progression rate in patients...
November 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/29108995/cd1d-is-a-novel-cell-surface-marker-for-human-monocytic-myeloid-derived-suppressor-cells-with-t-cell-suppression-activity-in-peripheral-blood-after-allogeneic-hematopoietic-stem-cell-transplantation
#5
Borim An, Ji-Young Lim, Suji Jeong, Dong-Mi Shin, Eun Young Choi, Chang-Ki Min, Seok-Ho Hong
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that regulate immune responses in cancer and various pathological conditions. However, the phenotypic and functional heterogeneity of human MDSCs represents a major hurdle for the development of therapeutic strategies targeting or regulating MDSCs in tumor progression, inflammation, and graft-versus-host disease (GVHD). We previously shown that circulating HLA-DR(-)CD14(+) monocytic MDSCs are a major contributor to clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT)...
November 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29104473/the-inhibition-of-indoleamine-2-3-dioxygenase-1-by-connexin-43
#6
Han-Chen Lin, Chih-Jen Yang, Yu-Diao Kuan, Wei-Kuang Wang, Wen-Wei Chang, Che-Hsin Lee
Upregulation of connexin 43 (Cx43) showed potential in enhancing immune surveillance that was suppressed in the tumor microenvironment. The expression of indoleamine 2, 3-dioxygenase (IDO) is one of the crucial factors contributing to tumor immune tolerance by depletion of tryptophan and IDO-mediated tryptophan metabolites. Here, we aim to investigate the role of Cx43 in IDO production in murine tumor by using Cx43 inducers. Resveratrol (trans-3, 5, 4 '-trihydroxystilbene) is a natural plant-derived polyphenol possessing positive effect against cancer...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29076586/cancer-and-normal-adipose-derived-mesenchymal-stem-cells-ascs-do-they-have-differential-effects-on-tumor-and-immune-cells
#7
Mahboobeh Razmkhah, Zahra Mansourabadi, Maryam Al-Sadat Mohtasebi, Abdol-Rasoul Talei, Abbas Ghaderi
Adipose-derived mesenchymal stem cells (ASCs) are known to have immunomodulatory properties through soluble factors or by direct cell-to-cell contact. This study aimed to assess the expression of HLA-G and IDO activity in breast cancer and normal ASCs and to see if ASC is capable of modulating both tumor cells and immune system cells in vitro. ASCs were enzymatically isolated from 15 breast cancer patients and 10 normal individuals. Then they were cultured, and the impact of their conditioned media on the movement of the MDA-MB-231 breast cancer cell line was studied in wound healing scratch assay...
October 27, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29066694/-clinical-evaluation-of-indoleamine-2-3-dioxygenase-in-the-serum-of-patients-with-locally-advanced-breast-cancer-during-mohs-paste-treatment
#8
Hitomi Kubota, Kenichi Sakurai, Shigeru Fujisaki, Yukiko Hara, Shuhei Suzuki, Keita Adachi, Ryouichi Tomita, Katsuhisa Enomoto, Tomohiro Hirano, Reina Saga, Makoto Makishima
Locally advanced breast cancer lesions often compromise patients' quality of life(QOL). Mohs paste is a histopathological fixative with zinc chloride as the main ingredient. It is applied when performing chemosurgery for skin tumors. In recent years, this paste has reportedly been very effective for the control of various symptoms of skin metastases in inoperable advanced cancers, such as pungent odor and hemorrhage, in the field of palliative care. We evaluated the clinical significance of indoleamine 2, 3-dioxygenase(IDO)in the serum of patients with locally advanced breast cancer during Mohs paste treatment...
October 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29066687/-indoleamine-2-3-dioxygenase-activity-during-letrozol-therapy-for-an-elderly-breast-cancer-patient
#9
Kenichi Sakurai, Shigeru Fujisaki, Hitomi Kubota, Yukiko Hara, Shuhei Suzuki, Keita Adachi, Ryouichi Tomita, Katsuhisa Enomoto, Tomohiro Hirano, Reina Saga, Makoto Makishima
We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)during letrozol therapy for an elderly patient with locally advanced breast cancer. IDO activity was measured by the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn levels were measured using high performance liquid chromatography(HPLC). Serum Trp/Kyn levels of the patient before endocrine therapy were lower than those after endocrine therapy. IDO activity decreased after endocrine therapy and correlat- ed with the number of metastatic lymph node lesions during letrozol therapy...
October 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29066685/-indoleamine-2-3-dioxygenase-activity-during-fulvestrant-therapy-for-aromatase-inhibitor-resistant-metastatic-breast-cancer
#10
Kenichi Sakurai, Shigeru Fujisaki, Hitomi Kubota, Yukiko Hara, Shuhei Suzuki, Keita Adachi, Ryouichi Tomita, Katsuhisa Enomoto, Tomohiro Hirano, Reina Saga, Makoto Makishima
We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)for breast cancer patients between different clinical stages and patient ages. IDO activity was measured by the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn levels were measured using high performance liquid chromatography(HPLC). Serum Trp/Kyn levels in Stage IV breast cancer patients were lower than in patients at other stages. Serum Trp/Kyn levels of breast cancer patients over the age of 70 years were lower than in patients under the age of 69 years...
October 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29057249/indoleamine-2-3-dioxygenase-and-survivin-peptide-vaccine-combined-with-temozolomide-in-metastatic-melanoma
#11
Nikolaj Juul Nitschke, Jon Bjoern, Trine Zeeberg Iversen, Mads Hald Andersen, Inge Marie Svane
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) and survivin have been identified as potential targets for cancer vaccination. In this phase II study a vaccine using the peptides Sur1M2 and IDO5 was combined with the chemotherapy temozolomide (TMZ) for treatment of metastatic melanoma patients. The aim was to simultaneously target several immune inhibiting mechanisms and the highly malignant cells expressing survivin. METHODS: HLA-A2 positive patients with advanced malignant melanoma were treated biweekly with 150 mg/m(2) TMZ daily for 7 days followed by subcutaneous vaccination with 250 µg of each peptide in 500 µL Montanide solution at day 8...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/29054599/indoleamine-2-3-dioxygenase-expression-in-primary-cutaneous-melanoma-correlates-with-breslow-thickness-and-is-of-significant-prognostic-value-for-progression-free-survival
#12
Felicia Rubel, Johannes S Kern, Kristin Technau-Hafsi, Sibylle Uhrich, Kaethe Thoma, Georg Häcker, Nikolas von Bubnoff, Frank Meiss, Dagmar von Bubnoff
The enzyme indoleamine 2,3-dioxygenase (IDO) is emerging as a facilitator of cancer development through its effects on cancer-associated inflammation. Recent studies report a significant improvement of the response rates in melanoma patients to PD-1 antibodies when IDO-inhibitors were added to the regimen. Data on IDO-expression in primary human melanomas are however incomplete and conflicting. Here, we show that the level of IDO-expression in primary human melanoma cells significantly correlates with Breslow thickness (p = 0...
October 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29037255/objective-measurement-and-clinical-significance-of-ido1-protein-in-hormone-receptor-positive-breast-cancer
#13
Daniel E Carvajal-Hausdorf, Nikita Mani, Vamsidhar Velcheti, Kurt A Schalper, David L Rimm
BACKGROUND: Immunostimulatory therapies targeting immune-suppressive pathways produce durable responses in advanced solid tumors. Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting oxidoreductase that catalyzes the degradation of tryptophan to kynurenine. IDO induces immune tolerance by downregulating CD8+ and effector CD4+ T cell responses. IDO1, the most active isoform, is expressed in diverse tumor types and can be targeted using small molecule inhibitors. We used an objective, in situ assay to measure IDO1 in a collection of hormone receptor-positive breast cancers (HR+ BC)...
October 17, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28987965/emerging-targets-in-cancer-immunotherapy
#14
REVIEW
Samantha Burugu, Amanda R Dancsok, Torsten O Nielsen
The first generation of immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1) targeted natural immune homeostasis pathways, co-opted by cancers, to drive anti-tumor immune responses. These agents led to unprecedented results in patients with previously incurable metastatic disease and may become first-line therapies for some advanced cancers. However, these agents are efficacious in only a minority of patients. Newer strategies are becoming available that target additional immunomodulatory mechanisms to activate patients' own anti-tumor immune responses...
October 5, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28978540/functional-vitamin-b-6-status-and-long-term-mortality-in-renal-transplant-recipients
#15
Isidor Minović, Anna van der Veen, Martijn van Faassen, Ineke J Riphagen, Else van den Berg, Claude van der Ley, António W Gomes-Neto, Johanna M Geleijnse, Manfred Eggersdorfer, Gerjan J Navis, Ido P Kema, Stephan Jl Bakker
Background: Low plasma concentrations of pyridoxal 5'-phosphate (PLP) are common in renal transplant recipients (RTRs) and confer increased risk of long-term mortality. To our knowledge, it is not known whether low plasma PLP concentrations have functional (i.e., intracellular) consequences and, if so, whether such consequences are associated with increased risk of mortality.Objectives: We assessed the association of plasma PLP with functional vitamin B-6 status and explored the potential association of functional vitamin B-6 status with long-term mortality in RTRs...
October 4, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28941938/design-synthesis-and-biological-evaluation-of-8-substituted-6-hydrazonoindolo-2-1-b-quinazolin-12-6h-one-scaffolds-as-potential-cytotoxic-agents-ido-1-targeting-molecular-docking-studies
#16
Ramu Guda, Rajashekar Korra, Siripireddy Balaji, Rambabu Palabindela, Rakesh Eerla, Harikiran Lingabathula, Narsimha Reddy Yellu, Girijesh Kumar, Mamatha Kasula
Herein, we have reported the synthesis of 18 novel 8-substituted tryptanthrin analogues based on our earlier work. All these tryptanthrin analogues were well characterized by (1)H &(13)C NMR, FT-IR, Mass Spectrometry and Elemental Analysis. All these 8-substituted analogues were screened for their anti-oxidant activity by DPPH radical scavenging assay. Out of all the tested compounds, T(11), T(12), T(17) and T(18) showed potent anti-oxidant activity. The anti-cancer activity have been performed by using MTT assay protocol and their results depicts that compounds having the 4-pyridyl or 4-carboxyphenyl substituents at the 8th position of the tryptanthrin framework are found to be the most promising cytotoxic agent against A549, MCF-7 and HeLa human cancer cell lines compared to others as well as with the standard drug cisplatin...
October 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28903363/p53-prevent-tumor-invasion-and-metastasis-by-down-regulating-ido-in-lung-cancer
#17
Dongfang Tang, Lu Yue, Ruyong Yao, Lin Zhou, Yuqin Yang, Liming Lu, Wen Gao
In present study, we are to clear demonstrate the genetic evidence of IDO signaling's impact on invasion and metastasis in lung cancer. Here we examined IDO1 expression levels in non-small cell lung cancer (NSCLC) patients (64) tumor/normal pairs underwent RT-PCR and comprehensive histological, immunohistochemica and clinical analysis. The NSCLC cells stably expressing IDO1 was analyzed for migration and invasion assays and the regulatory mechanism in vitro and metastasis assays in vivo. As results, we reported that IDO1 expression increased by more than 3...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893628/a-combination-of-nanosystems-for-the-delivery-of-cancer-chemoimmunotherapeutic-combinations-1-methyltryptophan-nanocrystals-and-paclitaxel-nanoparticles
#18
P Calleja, J M Irache, C Zandueta, C Martínez-Oharriz, S Espuelas
IDO is an enzyme that tumors use to create a state of immunosupression. 1-d-methyltryptophan (1-MT) is an IDO pathway inhibitor. After being successfully evaluated in preclinical studies, current clinical trials are actually analyzing its efficacy as monotherapy or in combination with multiple chemotherapeutic agents such as paclitaxel. 1-MT very poor solubility in water and many other solvents precludes its ease parenteral administration. It is currently administered by oral route because high daily doses were well-tolerated and effectively inhibited the IDO activity although only 25% of dose was recovered in plasma...
September 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28886696/inhibition-of-pi3k-akt-mtor-pathway-sensitizes-endometrial-cancer-cell-lines-to-parp-inhibitors
#19
Charles-André Philip, Ido Laskov, Marie-Claude Beauchamp, Maud Marques, Oreekha Amin, Joanna Bitharas, Roy Kessous, Liron Kogan, Tahira Baloch, Walter H Gotlieb, Amber Yasmeen
BACKGROUND: Phosphatase and Tensin homolog (PTEN) is a tumor suppressor gene. Loss of its function is the most frequent genetic alteration in endometrioid endometrial cancers (70-80%) and high grade tumors (90%). We assessed the sensitivity of endometrial cancer cell lines to PARP inhibitors (olaparib and BMN-673) and a PI3K inhibitor (BKM-120), alone or in combination, in the context of their PTEN mutation status. We also highlighted a direct pathway linking PTEN to DNA repair. METHODS: Using endometrial cancer cellular models with known PTEN status, we evaluated their homologous recombination (HR) functionality by RAD51 foci formation assay...
September 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28798777/mesenchymal-stem-cells-promote-metastasis-of-lung-cancer-cells-by-downregulating-systemic-antitumor-immune-response
#20
Marina Gazdic, Bojana Simovic Markovic, Nemanja Jovicic, Maja Misirkic-Marjanovic, Valentin Djonov, Vladimir Jakovljevic, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
Since majority of systemically administered mesenchymal stem cells (MSCs) become entrapped within the lungs, we used metastatic model of lung cancer, induced by intravenous injection of Lewis lung cancer 1 (LLC1) cells, to investigate the molecular mechanisms involved in MSC-mediated modulation of metastasis. MSCs significantly augmented lung cancer metastasis, attenuate concentrations of proinflammatory cytokines (TNF-α, IL-17), and increase levels of immunosuppressive IL-10, nitric oxide, and kynurenine in sera of LLC1-treated mice...
2017: Stem Cells International
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