Read by QxMD icon Read

Cancer and IDO

Cara C Schafer, Yong Wang, Kenneth P Hough, Anandi Sawant, Stefan C Grant, Victor J Thannickal, Jaroslaw Zmijewski, Selvarangan Ponnazhagan, Jessy S Deshane
Indoleamine 2,3-dioxygenase (IDO) has been implicated in immune evasion by tumors. Upregulation of this tryptophan (Trp)-catabolizing enzyme, in tumor cells and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME), leads to Trp depletion that impairs cytotoxic T cell responses and survival; however, exact mechanisms remain incompletely understood. We previously reported that a combination therapy of gemcitabine and a superoxide dismutase mimetic promotes anti-tumor immunity in a mouse model of lung cancer by inhibiting MDSCs, enhancing polyfunctional response of CD8+ memory T cells, and extending survival...
September 26, 2016: Oncotarget
Andrea Petretto, Grazia Carbotti, Elvira Inglese, Chiara Lavarello, Maria Pia Pistillo, Valentina Rigo, Michela Croce, Luca Longo, Stefania Martini, Paola Vacca, Silvano Ferrini, Marina Fabbi
IL-27, a member of the IL-12-family of cytokines, has shown anti-tumor activity in several pre-clinical models due to anti-proliferative, anti-angiogenic and immune-enhancing effects. On the other hand, IL-27 demonstrated immune regulatory activities and inhibition of auto-immunity in mouse models. Also, we reported that IL-27, similar to IFN-γ, induces the expression of IL-18BP, IDO and PD-L1 immune regulatory molecules in human cancer cells. Here, a proteomic analysis reveals that IL-27 and IFN-γ display a broad overlap of functions on human ovarian cancer cells...
September 24, 2016: Oncotarget
Elina Timosenko, Hemza Ghadbane, Jonathan D Silk, Dawn Shepherd, Uzi Gileadi, Lauren J Howson, Robert Laynes, Qi Zhao, Robert L Strausberg, Lars R Olsen, Stephen Taylor, Francesca M Buffa, Richard Boyd, Vincenzo Cerundolo
Tryptophan degradation is an immune escape strategy shared by many tumors. However, cancer cells' compensatory mechanisms remain unclear. We demonstrate here that a shortage of tryptophan caused by expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) resulted in ATF4-dependent upregulation of several amino acid transporters, including SLC1A5 and its truncated isoforms. which in turn enhanced tryptophan and glutamine uptake. Importantly, SLC1A5 failed to be up-regulated in resting human T cells kept under low tryptophan conditions, but was enhanced upon cognate antigen T cell receptor engagement...
September 20, 2016: Cancer Research
Ido Laskov, Paul Abou-Nader, Oreekha Amin, Charles-Andre Philip, Marie-Claude Beauchamp, Amber Yasmeen, Walter H Gotlieb
PURPOSE: Epithelial-mesenchymal transition (EMT) is a critical process for cancer metastasis and recurrence. Metformin, an effective oral antidiabetic drug, has been associated with decreased cancer risk and mortality. In this pilot study, we started to evaluate the effect of metformin on EMT in vivo and in vitro in endometrial cancer (EC). METHODS: Endometrial cancer cell lines and freshly isolated EC tumor specimens were used to assess EMT after metformin treatment...
September 2016: International Journal of Gynecological Cancer
Ivan H Chan, Victoria Wu, Melissa Bilardello, Brett Jorgenson, Harminder Bal, Scott McCauley, Peter Van Vlasselaer, John B Mumm
IL-10 has been classically defined as a broad-spectrum immunosuppressant and is thought to facilitate the development of regulatory CD4(+) T cells. IL-10 is believed to represent one of the major suppressive factors secreted by IDO(+)FoxP3(+)CD4(+) Tregs. Contrary to this view, we have previously reported that PEGylated recombinant IL-10 (PEG-rIL-10) treatment of mice induces potent IFNγ and CD8(+) T-cell-dependent antitumor immunity. This hypothesis is currently being tested in clinical trials and we have reported that treatment of cancer patients with PEG-rHuIL-10 results in inhibition and regression of tumor growth as well as increased serum IFNγ...
July 2016: Oncoimmunology
Matt Crook, Awani Upadhyay, Liyana J Ido, Wendy Hanna-Rose
Identification of pro-cell-survival signaling pathways has implications for cancer, cardiovascular and neurodegenerative disease. We show that the Caenorhaditis elegans epidermal growth factor receptor LET-23 has a pro-survival function in counteracting excitotoxicity, and we identify novel molecular players required for this pro-survival signaling. uv1 sensory cells in the C. elegans uterus undergo excitotoxic death in response to activation of the OSM-9/OCR-4 TRPV channel by the endogenous agonist nicotinamide...
September 7, 2016: G3: Genes—Genomes—Genetics
Charlotte S Lo, Sanaz Sanii, David R Kroeger, Katy Milne, Aline Talhouk, Derek S Chiu, Kurosh Rahimi, Patricia A Shaw, Blaise A Clarke, Brad H Nelson
PURPOSE: Some forms of chemotherapy can enhance anti-tumor immunity through immunogenic cell death, resulting in increased T cell activation and tumor infiltration. Such effects could potentially sensitize tumors to immunotherapies, including checkpoint blockade. We investigated whether platinum- and taxane-based chemotherapy for ovarian cancer induces immunological changes consistent with this possibility. METHODS: Matched pre- and post-neoadjuvant chemotherapy tumor samples from 26 high-grade serous carcinoma (HGSC) patients were analyzed by immunohistochemistry (IHC) for a large panel of immune cells and associated factors...
September 6, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yanqi Ye, Jinqiang Wang, Quanyin Hu, Gabrielle M Hochu, Hongliang Xin, Chao Wang, Zhen Gu
Despite the promising efficacy of immunoregulation in cancer therapy, the clinical benefit has been restricted by inefficient infiltration of lymphocytes in the evolution of immune evasion. Also, immune-related adverse events have often occurred due to the off-target binding of therapeutics to normal tissues after systematic treatment. In light of this, we have developed a synergistic immunotherapy strategy that locally targets the immunoinhibitory receptor programmed cell death protein 1 (PD1) and immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) for the treatment of melanoma through a microneedle-based transcutaneous delivery approach...
September 27, 2016: ACS Nano
O M Kolawole, K T Olatunji, K A Durowade
BACKGROUND: Human papillomavirus (HPV) has been implicated as one of the principal causes of cervical cancer, which is the second highest cause of cancer deaths among Nigerian women. OBJECTIVE: This study was aimed at determining the presence of HPV DNA in abnormal cervical cytology of a group of women who were screened using Papanicolaou staining technique. METHODOLOGY: A total of 200 women attending the Obstetrics and Gynaecology clinic of the Federal Teaching Hospital, Ido-Ekiti, were screened by means of conventional Pap smear screening, while positive samples underwent molecular analyses by means of DNA isolation techniques and polymerase chain reaction (PCR)...
2016: Journal of Preventive Medicine and Hygiene
Kuangda Lu, Chunbai He, Nining Guo, Christina Chan, Kaiyuan Ni, Ralph R Weichselbaum, Wenbin Lin
Photodynamic therapy (PDT) can destroy local tumors and minimize normal tissue damage, but is ineffective at eliminating metastases. Checkpoint blockade immunotherapy has enjoyed recent success in the clinic, but only elicits limited rates of systemic antitumor response for most cancers due to insufficient activation of the host immune system. Here we describe a treatment strategy that combines PDT by a new chlorin-based nanoscale metal-organic framework (nMOF), TBC-Hf, and a small-molecule immunotherapy agent that inhibits indoleamine 2,3-dioxygenase (IDO), encapsulated in the nMOF channels to induce systemic antitumor immunity...
September 28, 2016: Journal of the American Chemical Society
Josephine F Trott, Jeffrey Kim, Omran Abu Aboud, Hiromi Wettersten, Benjamin Stewart, Grace Berryhill, Francisco Uzal, Russell C Hovey, Ching-Hsien Chen, Katie Anderson, Ashley Graef, Aaron L Sarver, Jaime F Modiano, Robert H Weiss
Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro...
August 27, 2016: Oncotarget
Igal Kushnir, Ido Wolf
Nivolumab, a programmed death 1 (PD1) inhibitor, belongs to a family of drugs known as immune checkpoint inhibitors that share a similar toxicity profile, which includes rash, pruritus, colitis, hepatitis, pneumonitis and thyroid dysfunction. Nivolumab has a proven efficacy in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. We present the case of a 67-year-old male patient with metastatic squamous cell carcinoma of the lung who suffered from a massive pericardial effusion secondary to treatment with nivolumab, which he began in June 2015...
August 24, 2016: Cardiology
Guido A Gualdoni, Dietmar Fuchs, Gerhard J Zlabinger, Johanna M Gostner
BACKGROUND: Resveratrol is a polyphenol compound found in various nutrients that was shown to have immunomodulatory, anti-cancerogenic, and cardioprotective effects. The regulation of indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme in inflammatory tryptophan metabolism, has been proposed to be involved in resveratrol's biological effects. These observations, however, rely on in vitro findings and animal studies. Therefore, we assessed the impact of resveratrol on tryptophan metabolism after oral intake in humans...
October 2016: Pharmacological Reports: PR
Dawei Shou, Liang Wen, Zhenya Song, Jian Yin, Qiming Sun, Weihua Gong
Myeloid-derived suppressor cells (MDSCs) play a pivotal role in promoting tumor growth and metastasis and can even decrease the efficacy of immunotherapy. In breast cancer, MDSCs are recruited mainly by breast cancer cells to form a tumor-favoring microenvironment to suppress the anti-tumor immune response. In addition, MDSCs can react directly with breast cancer cells. In this paper, we describe several ways to recruit MDSCs in breast cancer, including breast cancer cell-derived cytokines and chemokines. The intracellular pathways in MDSCs during recruitment are classified as the STAT3-NF-κB-IDO pathway, the STAT3/IRF-8 pathway and the PTEN/Akt pathway...
August 17, 2016: Oncotarget
Michael D Lovelace, Bianca Varney, Gayathri Sundaram, Nunzio F Franco, Mei Li Ng, Saparna Pai, Chai K Lim, Gilles J Guillemin, Bruce J Brew
The kynurenine pathway (KP) is the major metabolic pathway of the essential amino acid tryptophan (TRP). Stimulation by inflammatory molecules, such as interferon-γ (IFN-γ), is the trigger for induction of the KP, driving a complex cascade of production of both neuroprotective and neurotoxic metabolites, and in turn, regulation of the immune response and responses of brain cells to the KP metabolites. Consequently, substantial evidence has accumulated over the past couple of decades that dysregulation of the KP and the production of neurotoxic metabolites are associated with many neuroinflammatory and neurodegenerative diseases, including Parkinson's disease, AIDS-related dementia, motor neurone disease, schizophrenia, Huntington's disease, and brain cancers...
2016: Frontiers in Immunology
Tomoko Inoue, Katsuyuki Adachi, Kei Kawana, Ayumi Taguchi, Takeshi Nagamatsu, Asaha Fujimoto, Kensuke Tomio, Aki Yamashita, Satoko Eguchi, Haruka Nishida, Hiroe Nakamura, Masakazu Sato, Mitsuyo Yoshida, Takahide Arimoto, Osamu Wada-Hiraike, Katsutoshi Oda, Yutaka Osuga, Tomoyuki Fujii
Cancer-associated fibroblasts (CAFs) play an important role in cancer expansion and progression in tumor microenvironment (TME), via both direct and indirect interactions. Natural killer (NK) cells play a crucial role in anticancer immunity. We investigated the inhibitory effects of CAFs on NK cell activity. CAFs were isolated from endometrial cancer tissue, while normal endometrial fibroblasts (NEFs) were obtained from normal endometrium with no pathological abnormality. NK cells were obtained from allogenic healthy volunteers...
October 2016: International Journal of Oncology
Syed S Mahmood, Farhad Abtahian, Annemarie E Fogerty, Philip Cefalo, Cheryl MacKay, Michael R Jaff, Ido Weinberg
BACKGROUND: Patients with metastatic carcinoma and venous thromboembolism commonly have contraindications to anticoagulation that prompts use of retrievable inferior vena cava filters. OBJECTIVES: The aim of this study was to compare the pattern of inferior vena cava filter use, anticoagulation management and development of inferior vena cava filter related complications in patients with localized versus metastatic carcinoma. METHODS: We conducted a retrospective cohort study of inferior vena cava filter use at a tertiary referral hospital between January 1, 2009 and December 31, 2011...
July 28, 2016: American Journal of Medicine
Adrian M Seifert, Shan Zeng, Jennifer Q Zhang, Teresa S Kim, Noah A Cohen, Michael J Beckman, Benjamin D Medina, Joanna H Maltbaek, Jennifer K Loo, Megan H Crawley, Ferdinand Rossi, Peter Besmer, Cristina R Antonescu, Ronald P DeMatteo
PURPOSE: Tyrosine kinase inhibitors are effective in gastrointestinal stromal tumor (GIST), but often are of transient benefit as resistance commonly develops. Immunotherapy, particularly blockade of the inhibitory receptor programmed death 1 (PD-1) or the ligand programmed death ligand 1 (PD-L1), has shown effectiveness in a variety of cancers. The functional effects of PD-1/PD-L1 blockade are unknown in GIST. EXPERIMENTAL DESIGN: We analyzed tumor and matched blood samples from 85 patients with GIST and determined the expression of immune checkpoint molecules using flow cytometry...
July 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Kurt A Schalper, Daniel Carvajal-Hausdorf, Joseph McLaughlin, Mehmet Altan, Vamsidhar Velcheti, Patricia Gaule, Miguel F Sanmamed, Lieping Chen, Roy S Herbst, David L Rimm
PURPOSE: To determine the expression level, associations and biological role of PD-L1, IDO-1 and B7-H4 in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Using multiplexed quantitative immunofluorescence (QIF), we measured the levels of PD-L1, IDO-1, B7-H4 and different tumor infiltrating lymphoycte (TIL) subsets in 552 stages I-IV lung carcinomas from 2 independent populations. Associations between the marker levels, TILs and major clinico-pathological variables were determined...
July 20, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Paul B Larkin, Korrapati V Sathyasaikumar, Francesca M Notarangelo, Hiroshi Funakoshi, Toshikazu Nakamura, Robert Schwarcz, Paul J Muchowski
BACKGROUND: In mammals, the majority of the essential amino acid tryptophan is degraded via the kynurenine pathway (KP). Several KP metabolites play distinct physiological roles, often linked to immune system functions, and may also be causally involved in human diseases including neurodegenerative disorders, schizophrenia and cancer. Pharmacological manipulation of the KP has therefore become an active area of drug development. To target the pathway effectively, it is important to understand how specific KP enzymes control levels of the bioactive metabolites in vivo...
November 2016: Biochimica et Biophysica Acta
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"