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Cancer immunotherapy

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https://www.readbyqxmd.com/read/28319781/systematic-study-of-imidazoles-inhibiting-ido1-via-the-integration-of-molecular-mechanics-and-quantum-mechanics-calculations
#1
Yi Zou, Fang Wang, Yan Wang, Wenjie Guo, Yihua Zhang, Qiang Xu, Yisheng Lai
Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as an attractive target for cancer immunotherapy. To rationalize the detailed interactions between IDO1 and its inhibitors at the atomic level, an integrated computational approach by combining molecular mechanics and quantum mechanics methods was employed in this report. Specifically, the binding modes of 20 inhibitors was initially investigated using the induced fit docking (IFD) protocol, which outperformed other two docking protocols in terms of correctly predicting ligand conformations...
March 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28319731/stimulating-cd27-to-quantitatively-and-qualitatively-shape-adaptive-immunity-to-cancer
#2
REVIEW
Timothy Nj Bullock
The capacity of the immune system to recognize and respond to tumors has been appreciated for over 100 years. However, clinical success has largely depended on the elucidation of the positive and negative regulators of effector cells after their activation via the antigen cell receptor. On the one hand, effector cells upregulate checkpoint molecules that are thought to play a role in limiting immunopathology. On the other, second and third waves of costimulation are often required to promote the expansion, survival and differentiation of effector cells...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319049/resisting-fatal-attraction-a-glioma-oncometabolite-prevents-cd8-t-cell-recruitment
#3
Liliana E Lucca, David A Hafler
Immunotherapy has emerged as a potent approach for treating aggressive cancers, such as non-small-cell lung tumors and metastatic melanoma. Clinical trials are now in progress for patients with malignant gliomas; however, a better understanding of how these tumors escape immune surveillance is required to enhance antitumor immune responses. With gliomas, the recruitment of CD8+ T cells to the tumor is impaired, in part preventing containment or elimination of the tumor. In this issue of the JCI, Kohanbash and colleagues present an elegant dissection of how gliomas exploit an enzymatic activity acquired through a common mutation to abrogate the migration of CD8+ T cells to the tumor...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28319047/isocitrate-dehydrogenase-mutations-suppress-stat1-and-cd8-t-cell-accumulation-in-gliomas
#4
Gary Kohanbash, Diego A Carrera, Shruti Shrivastav, Brian J Ahn, Naznin Jahan, Tali Mazor, Zinal S Chheda, Kira M Downey, Payal B Watchmaker, Casey Beppler, Rolf Warta, Nduka A Amankulor, Christel Herold-Mende, Joseph F Costello, Hideho Okada
Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318951/a-comprehensive-analysis-of-programmed-cell-death-ligand-1-expression-with-the-clone-sp142-antibody-in-non-small-cell-lung-cancer%C3%A2-patients
#5
Kazuki Takada, Gouji Toyokawa, Tatsuro Okamoto, Mototsugu Shimokawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Fumihiro Shoji, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND: Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with anti-PD-1 therapy currently the standard treatment for non-small-cell lung cancer (NSCLC) patients after the failure of first-line chemotherapy treatment. The recent phase II POPLAR and phase III OAK studies showed that atezolizumab, a representative PD-L1 inhibitor, exhibited a survival benefit compared with standard therapy in patients with NSCLC...
March 2, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28318556/natural-killer-cells-in-placentation-and-cancer-implications-for-hypertension-during-pregnancy
#6
Heather Yvonne Small, Denise C Cornelius, Tomasz J Guzik, Christian Delles
Hypertension during pregnancy is the most common medical condition encountered during gestation. Despite this, knowledge of the mechanisms that underlie the disease and the development of new therapies are limited. Hypertension during pregnancy and some forms of cancer confer an increased risk to the development of cardiovascular disease later in life; one mechanism which may link these conditions is the involvement of natural killer (NK) cells. Whilst immunology and immunotherapy are well-developed areas in oncology; the complex mechanisms of the immune system in health and disease at the maternal-fetal interface are less well-defined...
March 7, 2017: Placenta
https://www.readbyqxmd.com/read/28318493/-bipolar-disorders-in-oncology-characteristics-and-management
#7
Michel Reich, Nuria Kotecki
Bipolar disorders belong to the spectrum of mood disorders and represent a serious psychiatric comorbidity. Behaviors adopted by bipolar patients can foster cancer occurrence but also impact its management, especially during acute depressive or manic episode. Oncologists must adapt their protocols in order to obtain the best compliance for treatment and avoid any possible mood destabilization, with the inherent risk of suicidal attempt. Potential interactions between mood-stabilizing agents (lithium, divalproate, atypical antipsychotics, and anticonvulsivants) and oncologic treatment (chemotherapy, targeted therapy, immunotherapy, corticotherapy) will be particularly watched...
March 15, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28318336/are-tumor-infiltrating-lymphocytes-protagonists-or-background-actors-in-patient-selection-for-cancer-immunotherapy
#8
Federica Zito Marino, Paolo Antonio Ascierto, Giulio Rossi, Stefania Staibano, Marco Montella, Daniela Russo, Roberto Alfano, Alessandro Morabito, Gerardo Botti, Renato Franco
Tumor-infiltrating lymphocytes (TILs) are frequently observed in several tumors, reflecting the dynamic process of ''cancer immunoediting''. Prognostic and predictive values of TILs have been demonstrated in different cancers, proving their pivotal role in clinical outcome. In recent years, new therapies targeting immune checkpoint inhibitors, especially CTLA-4 and PD-1/PDL-1 pathways, have been introduced into clinical practice. In this context, TILs may even have a possible utility as a predictive biomarker for immunotherapy response...
March 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28316970/dgk-%C3%AE-a-checkpoint-in-cancer-mediated-immuno-inhibition-and-target-for-immunotherapy
#9
Elfriede Noessner
Immunotherapy is moving to the forefront of cancer treatments owing to impressive durable responses achieved with checkpoint blockade antibodies and adoptive T-cell therapy. Still, improvements are necessary since, overall, only a small percentage of patients benefit from current therapies. Here, I summarize evidence that DGK-α may represent an immunological checkpoint suppressing the activity of cytotoxic immunocytes in the tumor microenvironment. DGK-inhibitors can restore the antitumor function of tumor-suppressed adaptive and innate cytotoxic immunocytes...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28315555/checkpoint-inhibitors-common-immune-related-adverse-events-and-their-management%C3%A2
#10
RuthAnn Gordon, Mary Kate Kasler, Kristen Stasi, Yelena Shames, Mimma Errante, Kathryn Ciccolini, Anna Skripnik Lucas, Pam Raasch, Erica Fischer-Cartlidge
BACKGROUND: Immunotherapy, specifically the use of checkpoint inhibitors, offers patients with cancer an alternative to chemotherapy, targeting different pathways to destroy cancer cells. The side effects of immunotherapies, as well as their impact on normal tissue, need to be assessed and managed based on their mechanisms of action. OBJECTIVES: This article presents an overview of immune-related adverse events (AEs). 
. METHODS: Common immune-related toxicities, as well as rare and refractory toxicities, are reviewed...
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28315554/immunotherapy-exploring-the-state-of-the-science%C3%A2
#11
Pamela K Ginex, Kelly Brassil, Beth Ely
Immunotherapy research provides opportunities for nurse scientists and researchers to be at the forefront of the changing landscape of cancer treatment. As these therapies continue to develop, current initiatives will seek to support nurses in clinical practice who must provide safe, evidence-based care and education to patients and their families. This article explores the current state of immunotherapy research and the ways in which continued research can help to advance nursing education and practice.
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28315552/cancer-immunotherapy-an-evidence-based-overview-and-implications-for-practice
#12
Virginia Bayer, Beau Amaya, Diane Baniewicz, Colleen Callahan, Lisa Marsh, Asia S McCoy
BACKGROUND: Significant research progress has been made in immunotherapies since the mid-1990s, and this rapid evolution necessitates evidence-based education on immunotherapies, their pathophysiology, and their toxicities to provide safe, effective care.
. OBJECTIVES: The aim of this article is to provide an evidence-based overview, with implications for practice, of checkpoint inhibitors, monoclonal antibodies, oncolytic viral therapies, and chimeric antigen receptor T-cell therapies...
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28315541/hypophysitis-nursing-management-of-immune-related-adverse-events%C3%A2
#13
Adrienne Vazquez
Immunotherapy can treat cancer and prevent future cancer relapse by enhancing the body's immune system. With novel immunotherapeutic agents like checkpoint inhibitors come unique immune-related adverse events. Hypophysitis, one of the lesser known immune-related complications, may be observed in patients receiving checkpoint inhibitors. Although the acute symptoms of immune-related hypophysitis may be managed with attentive monitoring and high-dose corticosteroids, lifelong hormone substitution therapy may be warranted...
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28315073/mechanisms-of-resistance-to-immune-checkpoint-antibodies
#14
Rodrigo N Ramos, Eliane Piaggio, Emanuela Romano
Immunotherapy using checkpoint inhibitors has changed the way we treat several aggressive cancers such as melanoma, non-small cell lung and head & neck cancers, among others, with durable responses achieved in the metastatic setting. However, unfortunately, the vast majority of patients do not respond to checkpoint inhibition therapy and a minority of patients, who do respond to treatment, develop secondary resistance and experience relapse by mechanisms still inadequately understood. Emerging evidence shows that alterations in multiple signaling pathways are involved in primary and/or secondary resistance to checkpoint inhibition...
March 18, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28315060/results-of-a-phase-ib-trial-of-combination-immunotherapy-with-a-cd8-%C3%A2-t-cell-eliciting-vaccine-and-trastuzumab-in-breast-cancer-patients
#15
G Travis Clifton, Jennifer K Litton, Karen Arrington, Sathibalan Ponniah, Nuhad K Ibrahim, Victor Gall, Gheath Alatrash, George E Peoples, Elizabeth A Mittendorf
BACKGROUND: CD8+ T cell-eliciting vaccines are being investigated in breast cancer patients. Preclinical data showed that trastuzumab increases the susceptibility of tumor cells to lysis by vaccine-generated CD8+ T cells, suggesting potential benefit of a combination immunotherapy strategy. The current trial was undertaken to demonstrate the safety of this approach. METHODS: This study was designed as a dose-escalation trial enrolling clinically disease-free, human leukocyte antigen A2+ or A3+ , human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients...
March 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28314956/evolution-of-mhc-based-technologies-used-for-detection-of-antigen-responsive-t-cells
#16
REVIEW
Amalie Kai Bentzen, Sine Reker Hadrup
T cell-mediated recognition of peptide-major histocompatibility complex (pMHC) class I and II molecules is crucial for the control of intracellular pathogens and cancer, as well as for stimulation and maintenance of efficient cytotoxic responses. Such interactions may also play a role in the development of autoimmune diseases. Novel insights into this mechanism are crucial to understanding disease development and establishing new treatment strategies. MHC multimers have been used for detection of antigen-responsive T cells since the first report by Altman et al...
March 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28314751/identification-of-glycopeptides-as-post-translationally-modified-neoantigens-in-leukemia
#17
Stacy A Malaker, Sarah A Penny, Lora G Steadman, Paisley T Myers, Justin Loke, Manoj Raghavan, Dina L Bai, Jeffery Shabanowitz, Donald Hunt, Mark Cobbold
Leukemias are highly immunogenic but have a low mutational load, providing few mutated peptide targets. Thus, the identification of alternative neoantigens is a pressing need. Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues...
March 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28314352/immunotherapy-for-gastrointestinal-cancer
#18
(no author information available yet)
No abstract text is available yet for this article.
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314294/mismatch-repair-protein-deficiency-is-a-risk-factor-for-aberrant-expression-of-hla-class-i-molecules-a-putative-adaptive-immune-escape-phenomenon
#19
Terufumi Kubo, Yoshihiko Hirohashi, Kazuhiko Matsuo, Tomoko Sonoda, Hiroki Sakamoto, Kiyoshi Furumura, Tomohide Tsukahara, Takayuki Kanaseki, Munehide Nakatsugawa, Hiroshi Hirano, Tomohisa Furuhata, Ichiro Takemasa, Tadashi Hasegawa, Toshihiko Torigoe
Accumulating evidence indicates that immune checkpoint inhibition-mediated cancer immunotherapies greatly improve the prognosis of certain types of cancer. This approach is now becoming a standard therapy, joining surgery, radiotherapy, and chemotherapy. Because the costs of antibody drugs are now a socioeconomic burden in many countries, an urgent need in cancer immunotherapy is the identification of relevant biomarkers that can predict therapy efficacy. Recent studies have reported that colorectal adenocarcinoma with hereditary or sporadic deficiency in mismatch repair (MMR) proteins has high antigenicity and that detection of these proteins could be a promising way to estimate clinical response...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28306559/immunotherapy-a-new-treatment-paradigm-in-bladder-cancer
#20
Nicole N Davarpanah, Akira Yuno, Jane B Trepel, Andrea B Apolo
PURPOSE OF REVIEW: T-cell checkpoint blockade has become a dynamic immunotherapy for bladder cancer. In 2016, atezolizumab, an immune checkpoint inhibitor, became the first new drug approved in metastatic urothelial carcinoma (mUC) in over 30 years. In 2017, nivolumab was also approved for the same indication. This overview of checkpoint inhibitors in clinical trials focuses on novel immunotherapy combinations, predictive biomarkers including mutational load and neoantigen identification, and an evaluation of the future of bladder cancer immunotherapy...
March 16, 2017: Current Opinion in Oncology
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