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Cancer and IDO

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https://www.readbyqxmd.com/read/29764164/immunoregulatory-antigens-novel-targets-for-cancer-immunotherapy
#1
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/29752722/a-new-cancer-immunotherapy-via-simultaneous-dc-mobilization-and-dc-targeted-ido-gene-silencing-using-an-immune-stimulatory-nanosystem
#2
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
#3
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/29742279/ethnicity-related-trends-in-gynecologic-malignancies-in-israel-1993-2013
#4
Nadav Michaan, Limor Gortzak-Uzan, Dan Grisario, Ido Laskov
OBJECTIVE: To describe trends and ethnic differences in incidence of gynecologic cancer in Israel. METHODS: In the present retrospective epidemiologic study, age-standardized rates (ASRs) rates of gynecologic malignancies that occurred between January 1, 1993, and December 31, 2013, were extracted from the Israeli National Cancer Registry. The annual percent change (APC) was calculated separately for Jewish and Arab patients for ovarian, endometrial, and cervical cancers...
May 9, 2018: International Journal of Gynaecology and Obstetrics
https://www.readbyqxmd.com/read/29730461/evolution-of-checkpoint-inhibitors-for-the-treatment-of-metastatic-gastric-cancers-current-status-and-future-perspectives
#5
REVIEW
Julien Taieb, Markus Moehler, Narikazu Boku, Jaffer A Ajani, Eduardo Yañez Ruiz, Min-Hee Ryu, Silke Guenther, Vikram Chand, Yung-Jue Bang
BACKGROUND: Standard treatment options for patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) are associated with limited efficacy and some toxicity. Recently, immunotherapy with antibodies that inhibit the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction has emerged as a new treatment option. This manuscript reviews early-phase and late-phase trials of immunotherapy in advanced GC/GEJC. METHODS: Searches for studies of immunotherapy in GC/GEJC were performed using PubMed, ClinicalTrials...
April 22, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29724044/mechanisms-of-intrinsic-tumor-resistance-to-immunotherapy
#6
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/29719533/high-indoleamine-2-3-dioxygenase-is-correlated-with-microvessel-density-and-worse-prognosis-in-breast-cancer
#7
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
https://www.readbyqxmd.com/read/29706548/the-energetics-and-physiological-impact-of-cohesin-extrusion
#8
Laura Vian, Aleksandra Pękowska, Suhas S P Rao, Kyong-Rim Kieffer-Kwon, Seolkyoung Jung, Laura Baranello, Su-Chen Huang, Laila El Khattabi, Marei Dose, Nathanael Pruett, Adrian L Sanborn, Andres Canela, Yaakov Maman, Anna Oksanen, Wolfgang Resch, Xingwang Li, Byoungkoo Lee, Alexander L Kovalchuk, Zhonghui Tang, Steevenson Nelson, Michele Di Pierro, Ryan R Cheng, Ido Machol, Brian Glenn St Hilaire, Neva C Durand, Muhammad S Shamim, Elena K Stamenova, José N Onuchic, Yijun Ruan, Andre Nussenzweig, David Levens, Erez Lieberman Aiden, Rafael Casellas
Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA...
April 24, 2018: Cell
https://www.readbyqxmd.com/read/29688039/mathematical-modelling-of-the-synergistic-combination-of-radiotherapy-and-indoleamine-2-3-dioxygenase-ido-inhibitory-immunotherapy-against-glioblastoma
#9
Arthur Chakwizira, Jonatan Ahlstedt, Henrietta Nittby Redebrandt, Crister Ceberg
OBJECTIVE: Recent research has shown that combining radiotherapy and immunotherapy can counteract the ability of cancer to evade and suppress the native immune system. To optimize the synergy of the combined therapies, factors such as radiation dose and fractionation must be considered, alongside numerous parameters resulting from the complexity of cancer-immune system interactions. It is instructive to use mathematical models to tackle this problem. METHODS: In this work, we adapted a model primarily to describe the synergistic effect between single-fraction radiotherapy and immunotherapy (1-methyl tryptophan) observed in previous experiments with glioblastoma-carrying rats...
April 24, 2018: British Journal of Radiology
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
#10
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...
April 17, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29643292/-a-case-of-postoperative-recurrent-gastric-cancer-resembling-esophageal-achalasia-diagnosed-by-staging-laparoscopy
#11
Masayuki Kabayama, Fumisato Sasaki, Hidehito Maeda, Shiho Arima, Shiroh Tanoue, Yuichiro Nasu, Shinichi Hashimoto, Shuji Kanmura, Jun Kadono, Akio Ido
A 65-year-old man underwent subtotal gastrectomy for advanced gastric cancer. The histological type of the cancer was signet-ring cell carcinoma, and the clinical stage was stage IB (T2N0M0). Three years after surgery, the patient had the following symptoms:dysphagia, odynophagia, and weight loss. Esophageal endoscopy and esophagography revealed a circular stenosis covered with the normal mucosa between the middle esophagus and the esophagogastric junction. Histologically, the samples obtained by staging laparoscopy revealed signet-ring cell carcinoma...
2018: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/29621426/tumor-infiltrating-treg-mdsc-and-ido-expression-associated-with-outcomes-of-neoadjuvant-chemotherapy-of-breast-cancer
#12
Fangxuan Li, Yang Zhao, Lijuan Wei, Shixia Li, Juntian Liu
BACKGROUND: Regulatory T cells(Tregs) and myeloid-derived suppressor cells(MDSCs) represent two immunosuppressive cell populations that are important in the establishment and maintenance of cancer immune tolerance. MDSCs can express IDO and promote immune tolerance via expansion of Treg cell. METHOD: We use needle biopsy breast cancer tissues prior to neoadjuvant chemotherapy(NCT) staining for CD33, Foxp3 and IDO by immunohistochemistry to evaluate whether they were correlated with subsequent treatment responses in breast cancer...
April 5, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29607498/1-l-mt-an-ido-inhibitor-prevented-colitis-associated-cancer-by-inducing-cdc20-inhibition-mediated-mitotic-death-of-colon-cancer-cells
#13
Xiuting Liu, Wei Zhou, Xin Zhang, Yang Ding, Qianming Du, Rong Hu
Indoleamine 2,3-dioxygenase 1 (IDO1), known as IDO, catabolizes tryptophan through kynurenine pathway, whose activity is correlated with impaired clinical outcome of colorectal cancer. Here we showed that 1-L-MT, a canonical IDO inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. Our results showed that inhibition of IDO decreased the transcription of CDC20, which resulted in G2/M cycle arrest of HCT-116 and HT-29. Furthermore, 1-L-MT induced mitochondria injuries and caused apoptotic cancer cells...
April 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29564182/updates-on-immunotherapy-for-colorectal-cancer
#14
REVIEW
Aparna Kalyan, Sheetal Kircher, Hiral Shah, Mary Mulcahy, Al Benson
Despite significant advances in standard of care therapies, the 5-year survival rate for metastatic colorectal cancer (CRC) remains around 12%. Immunotherapy has not provided the stellar advances in colorectal cancer that has been seen in other malignancies. Immunotherapy appears to play a pivotal role in microsatellite unstable CRC tumors where the response rates are profound. These results have led to FDA approval of pembrolizumab for MSI-H CRC tumors. Additional research into several new immune agents including IDO inhibitors, vaccine therapy and combinatorial agents are being evaluated for CRC...
February 2018: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29559741/indoleamine-2-3-dioxygenase-in-endometrial-cancer-a-targetable-mechanism-of-immune-resistance-in-mismatch-repair-deficient-and-intact-endometrial-carcinomas
#15
Anne Mills, Sara Zadeh, Emily Sloan, Zachary Chinn, Susan C Modesitt, Kari L Ring
Mismatch repair-deficient endometrial carcinomas are optimal candidates for immunotherapy given their high neoantigen loads, robust lymphoid infiltrates, and frequent PD-L1 expression. However, co-opting the PD-1/PD-L1 pathway is just one mechanism that tumors can utilize to evade host immunity. Another immune modulatory molecule that has been demonstrated in endometrial carcinoma is indoleamine 2,3-dioxygenase (IDO). We herein evaluate IDO expression in 60 endometrial carcinomas and assess results in relation to PD-L1 and mismatch repair status...
March 20, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29544515/next-generation-of-immune-checkpoint-therapy-in-cancer-new-developments-and-challenges
#16
REVIEW
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29543650/tryptophan-catabolites-along-the-indoleamine-2-3-dioxygenase-pathway-as-a-biological-link-between-depression-and-cancer
#17
Francisco S Barreto, Adriano J M Chaves Filho, Márcia C C R de Araújo, Manoel O de Moraes, Maria E A de Moraes, Michael Maes, David F de Lucena, Danielle S Macedo
Both depression and cancer are related to a dysregulation of inflammatory and immune pathways. Indeed, depression is associated with increased expression of interferon-γ, interleukin-1β, and tumor necrosis factor α (TNF-α). In contrast, reductions of the activity of major histocompatibility complex protein molecules - class I and class II and natural killer cells are also observed. Similarly, cancers present elevated levels of TNF-α, reduced major histocompatibility complex class I and II, and natural killer cells...
April 2018: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29500439/indoleamine-2-3-dioxygenase-expression-regulates-the-survival-and-proliferation-of-fusobacterium-nucleatum-in-thp-1-derived-macrophages
#18
Ying Xue, Han Xiao, Songhe Guo, Banglao Xu, Yuehua Liao, Yixian Wu, Ge Zhang
Fusobacterium nucleatum (Fn) is a tumor-associated obligate anaerobic bacterium, which has a role in the progression of colorectal cancer (CRC). Fn can invade and promote colon epithelial cells proliferation. However, how Fn survives and proliferates in its host cells remains largely unknown. In this study, we aimed to determine the molecular mechanisms underlying the morphology, survival, and proliferation of Fn in THP-1-derived macrophages (dTHP1). For the first time, we found that Fn is a facultative intracellular bacterium that can survive and limited proliferate in dTHP1 cells up to 72 h, and a live Fn infection can inhibit apoptosis of dTHP1 cells by activating the PI3K and ERK pathways...
March 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29498788/high-ido-1-expression-in-tumor-endothelial-cells-is-associated-with-response-to-immunotherapy-in-metastatic-renal-cell-carcinoma
#19
Andreas Seeber, Gerald Klinglmair, Josef Fritz, Fabian Steinkohl, Kai-Christian Zimmer, Friedrich Aigner, Wolfgang Horninger, Günther Gastl, Bettina Zelger, Andrea Brunner, Renate Pichler
Nivolumab belongs to the standard therapy in the second-line setting of metastatic renal cell carcinoma (mRCC). Although deep and long-lasting responses are seen in some patients, the majority of patients will further progress. PD-L1 is still under critical evaluation as a predictive biomarker. Thus, more accurate biomarkers are clearly warranted. Here, we investigated for the first time the predictive role of IDO-1, a negative immune-regulatory molecule, on clear cell RCC tissues of 15 patients undergoing nivolumab therapy...
March 2, 2018: Cancer Science
https://www.readbyqxmd.com/read/29494816/4-bromophenylhydrazinyl-benzenesulfonylphenylureas-as-indoleamine-2-3-dioxygenase-inhibitors-with-in-vivo-target-inhibition-and-anti-tumor-efficacy
#20
Shu-Yu Lin, Teng-Kuang Yeh, Jen-Shin Song, Ming-Shiu Hung, Ming-Fu Cheng, Fang-Yu Liao, An-Shiou Li, Shu-Ying Cheng, Li-Mei Lin, Chun-Hsien Chiu, Mine-Hsine Wu, Yi-Jyun Lin, Wenchi Hsiao, Manwu Sun, Yi-Hsin Wang, Chin-Hsiang Huang, Ya-Chu Tang, Hsin-Huei Chang, Zih-Ting Huang, Yu-Sheng Chao, Chuan Shih, Shiow-Lin Pan, Su-Ying Wu, Ching-Chuan Kuo, Shau-Hua Ueng
Indoleamine 2,3-dioxygenase is a heme-containing enzyme implicated in the down regulation of the anti-tumor immune response, and considered a promising anti-cancer drug target. Several pharmaceutical companies, including Pfizer, Merck, and Bristol-Myers Squibb, are known to be in pursuit of IDO inhibitors, and Incyte recently reported good results in the phase II clinical trial of the IDO inhibitor Epacadostat. In previous work, we developed a series of IDO inhibitors based on a sulfonylhydrazide core structure, and explored how they could serve as potent IDO inhibitors with good drug profiles...
April 2018: Bioorganic Chemistry
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