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Cancer and immune checkpoint

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https://www.readbyqxmd.com/read/28719552/immune-checkpoint-inhibitors-in-organ-transplant-patients
#1
Adam S Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant...
July 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28719380/comparison-of-different-antibody-clones-for-immunohistochemistry-detection-of-programmed-cell-death-ligand-1-pd-l1-on-non-small-cell-lung-carcinoma
#2
Edwin R Parra, Pamela Villalobos, Barbara Mino, Jaime Rodriguez-Canales
Programmed cell death ligand 1 (PD-L1) is a major immune checkpoint protein that mediates antitumor immune suppression and response. Preliminary data suggest that its detection using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded tissues may predict clinical response to PD-1/PD-L1 therapy. In diagnostic pathology, it is essential to count with a validated IHC that can reliably detect PD-L1-positive cases. The present study was conducted to compare and validate different PD-L1 commercial clones and identify which ones can be reliably used by surgical pathologist to detect PD-L1 expression in human cancer tissues...
July 17, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28719055/endocrine-toxicity-of-immune-checkpoint-inhibitors-essential-crosstalk-between-endocrinologists-and-oncologists
#3
REVIEW
Frédéric Illouz, Claire Briet, Lucie Cloix, Yannick Le Corre, Nathalie Baize, Thierry Urban, Ludovic Martin, Patrice Rodien
Two types of immune checkpoint inhibitors, both antibodies that target cytotoxic T-lymphocyte antigen-4 and those that target programmed cell death-protein 1, have been approved for use in melanoma, non-small-cell lung cancer, and renal cell carcinoma as first-line or second-line therapy. Their adverse events are primarily regarded as immune-related adverse events. We felt it was important to pinpoint and discuss certain preconceptions or misconceptions regarding thyroid dysfunction, hypophysitis, and diabetes induced by immune checkpoint inhibitors...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28718428/ifn-signaling-and-icb-resistance-time-is-on-tumor-s-side
#4
Alejandro López-Soto, Segundo Gonzalez, Alicia R Folgueras
Activation of antitumor immunity upon immune checkpoint blockade (ICB) is one of the most promising strategies in cancer therapy. However, ICB resistance is frequently observed in cancer preclinical models and patients. A recent report in Cell reveals that sustained interferon (IFN) signaling confers tumor resistance to ICB by inducing the expression of an immunosuppressive multigenic program.
March 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28716895/ctla4-promotes%C3%A2-tyk2-stat3-dependent-b-cell-oncogenecity
#5
Andreas Herrmann, Christoph Lahtz, Toshikage Nagao, Joo Y Song, Wing C Chan, Heehyoung Lee, Chanyu Yue, Thomas Look, Ronja Muelfarth, Wenzhao Li, Kurt Jenkins, John Williams, Lihua E Budde, Stephen J Forman, Larry W Kwak, Thomas Blankenstein, Hua Yu
Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is a well-established immune checkpoint for antitumor immune responses. The pro-tumorigenic function of CTLA4 is believed to be limited to T cell inhibition by countering the activity of the T cell co-stimulating receptor CD28. However, as we demonstrate here, there are two additional roles for CTLA4 in cancer, including via CTLA4 overexpression in diverse B cell lymphomas and in melanoma-associated B cells. CTLA4-CD86 ligation recruited and activated the JAK family member Tyk2, resulting in STAT3 activation and expression of genes critical for cancer immunosuppression and tumor growth and survival...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28716463/combination-strategies-on-the-basis-of-immune-checkpoint-inhibitors-in-non-small-cell-lung-cancer-where-do-we-stand
#6
REVIEW
Meng Qiao, Tao Jiang, Shengxiang Ren, Caicun Zhou
The era of immune checkpoint inhibitors, especially programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies in the treatment of advanced non-small-cell lung cancer (NSCLC) is coming. Because of the lack of the definite biomarkers to select the optimal responders, only approximately 20% of patients with advanced NSCLC would respond to single checkpoint inhibitors-based immunotherapy. Moreover, primary or acquired resistance to conventional therapies is inevitable in most cases. Thus, combinations are pushed to move forward to be an alternative strategy and surely, it would be a future direction...
June 23, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28716068/highlights-of-the-31st-annual-meeting-of-the-society-for-immunotherapy-of-cancer-sitc-2016
#7
REVIEW
James L Gulley, Elizabeth A Repasky, Laura S Wood, Lisa H Butterfield
Therapeutic efforts to engage the immune system against cancer have yielded exciting breakthroughs and a growing list of approved immune-based agents across a variety of disease states. Despite the early successes and durable responses associated with treatments such as immune checkpoint inhibition, there is still progress to be made in the field of cancer immunotherapy. The 31st annual meeting of the Society for Immunotherapy of Cancer (SITC 2016), which took place November 11-13, 2016 in National Harbor, Maryland, showcased the latest advancements in basic, translational, and clinical research focused on cancer immunology and immunotherapy...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28715649/excellent-response-to-anti-pd-1-therapy-in-a-patient-with-hepatocellular-carcinoma-case-report-and-review-of-literature
#8
Hirva Mamdani, Howard Wu, Bert H O'Neil, Amikar Sehdev
Hepatocellular carcinoma (HCC) is an aggressive cancer associated with high mortality worldwide. HCC develops in the setting of underlying cirrhosis due to chronic liver disease. Surgery is usually considered the treatment of choice for early disease; however, most patients have locally advanced or metastatic HCC at diagnosis in which case treatments are limited. Immune checkpoint blockade of programmed death receptor-1 (PD-1) pathway offers a potential treatment strategy based on the encouraging results of the phase I/II trial of nivolumab (Checkmate 040 trial)...
May 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28714919/overcoming-oncogenic-mediated-tumor-immunity-in-prostate-cancer
#9
REVIEW
Geoffrey Bryant, Lin Wang, David J Mulholland
Immunotherapy is being tested intensively in clinical trials for prostate cancer; it includes immune checkpoint inhibition, prostate specific antigen (PSA) vaccines and dendritic cell-based strategies. Despite increasing evidence for clinical responses, the consensus of multiple trials is that prostate cancers are poorly responsive to immunotherapy. Prostate cancer has a high degree of pathological and genetic heterogeneity compared to other cancer types, which may account for immunotherapeutic resistance. This hypothesis also implies that select types of prostate tumors may be differentially responsive to immune-based strategies and that the clinical stage, pathological grade and underlying genetic landscape may be important criteria in identifying tumors that respond to immune therapies...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28714780/atezolizumab-for-the-treatment-of-non-small-cell-lung-cancer
#10
Fernando C Santini, Charles M Rudin
The immune system can restrain or promote cancer development and growth. Antibodies targeting immune checkpoints have revolutionized cancer treatment. Among the best responses have been in non-small cell lung cancer (NSCLC) which is largely caused by chronic exposure to carcinogens; associated with high neoantigen creation and sensitization to immune recognition. Atezolizumab was the first approved antibody that targets the PD-1 ligand (PD-L1). Areas Covered: This drug profile article covers the basics of the cancer-immunity cycle and reviews some aspects of innate and adaptive immunology...
July 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28713682/predictive-biomarkers-of-immunotherapy-for-non-small-cell-lung-cancer-results-from-an-experts-panel-meeting-of-the-italian-association-of-thoracic-oncology
#11
REVIEW
Cesare Gridelli, Andrea Ardizzoni, Massimo Barberis, Federico Cappuzzo, Francesca Casaluce, Romano Danesi, Giancarlo Troncone, Filippo De Marinis
Unleashing the potential of immune system to fight cancer has become one of the main promising treatment modalities for advanced non-small cell lung cancer (NSCLC). The knowledge of numerous factors that come into play in the cancer-immunity cycle provide a wide range of potential therapeutic targets, including monoclonal antibodies that inhibits the programmed death-1 (PD-1) checkpoint pathway. Over the last two years, nivolumab, pembrolizumab and atezolizumab received approval for treatment of pretreated advanced NSCLC, and more recently, immunotherapy with pembrolizumab is the new standard of care as first-line in patients with high levels of programmed death-ligand 1 (PD-L1) expression...
June 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28707537/a-perspective-on-the-impact-of-radiation-therapy-on-the-immune-rheostat
#12
William H McBride, Ekambaram Ganapathy, Mi-Heon Lee, Jean P Nesseler, Christine Nguyen, Dörthe Schaue
The advent and success of immune checkpoint inhibitors (ICIs) in cancer treatment has broadened the spectrum of tumours that might be considered "immunogenic" and susceptible to immunotherapeutic (IT) intervention. Not all cancer types are sensitive, and not all patients with any given type respond. Combination treatment of ICIs with an established cytotoxic modality such as radiation therapy (RT) is a logical step towards improvement. For one, RT alone has been shown to be genuinely immunomodulatory and secondly pre-clinical data generally support combined ICI-RT approaches...
July 14, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28707500/noninvasive-imaging-of-immune-checkpoint-ligand-pd-l1-in-tumors-and-metastases-for-guiding-immunotherapy
#13
Samit Chatterjee, Wojciech G Lesniak, Sridhar Nimmagadda
Immunotherapy holds great promise in cancer treatment. The challenges in advancing immunotherapies lie in patient stratification and monitoring therapy. Noninvasive detection of immune checkpoint ligand PD-L1 can serve as an important biomarker for guidance and monitoring of immunotherapy. Here in, we provide an overview of our efforts to develop clinically translatable PD-L1-specific imaging agents for quantitative and real-time assessment of PD-L1 expression in tumor microenvironment.
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28707274/cancer-immunotherapies-are-they-as-effective-in-the-elderly
#14
Kate Poropatich, Joel Fontanarosa, Sandeep Samant, Jeffrey A Sosman, Bin Zhang
Almost two-thirds of all new cancer diagnoses are made in persons over the age of 65 years, yet it is unclear if age affects patient responsiveness to immunotherapy, which is increasingly becoming first-line therapy in advanced stages of different tumor types. Preclinical animal studies may be difficult to translate into humans since they frequently use young mice (2-3 months of age) equivalent to adolescent human subjects. Nevertheless, ex vivo studies from humans are concordant with mice tissue findings-older patients have an increased density of circulating regulatory immune cells and a decreased ratio of naïve-to-memory T cells...
July 13, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28707167/supportive-care-for-patients-undergoing-immunotherapy
#15
Bernardo Leon Rapoport, Ronwyn van Eeden, Vincent Sibaud, Joel B Epstein, Jean Klastersky, Matti Aapro, Devan Moodley
Immune checkpoint inhibitors, a new class of cancer therapeutic agents, play an important role in the management of melanoma, NSCLC, and other malignancies. A workshop organized by three MASCC Study Groups: Oral Care, Skin Toxicities, and Neutropenia, Infection, and Myelosuppression during the MASCC Annual Meeting held in Adelaide, Australia on 23-25 June, 2016 focused on the new class of anti-cancer therapeutic agents. Topics in the workshop included the mechanism of action and clinical uses of immune anti-CTL4 and anti-PD1 antibodies, checkpoint inhibitor toxicities, including skin adverse events, gastrointestinal toxicities, oral complications, pulmonary toxicities, and endocrinological and immune-related infections...
July 13, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28707078/ctla-4-expression-in-the-non-small-cell-lung-cancer-patient-tumor-microenvironment-diverging-prognostic-impact-in-primary-tumors-and-lymph-node-metastases
#16
Erna-Elise Paulsen, Thomas K Kilvaer, Mehrdad Rakaee, Elin Richardsen, Sigurd M Hald, Sigve Andersen, Lill-Tove Busund, Roy M Bremnes, Tom Donnem
The immune checkpoint receptor CTLA-4 plays a crucial part in negatively regulating T cell activation and maintaining self-tolerance. It is frequently overexpressed in a variety of malignancies, yet its prognostic impact in non-small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays from tumor tissue samples and evaluated the immunohistochemical expression of CTLA-4 in 536 patients with primary resected stage I-IIIA NSCLC. Expression of CTLA-4 was analyzed in tumor and stromal primary tumor tissue and in locoregional metastatic lymph nodes...
July 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28705302/the-value-of-immune-checkpoint-inhibitors-for-advanced-lung-cancer
#17
EDITORIAL
Akira Inoue
No abstract text is available yet for this article.
July 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/28705024/medi-4736-durvalumab-in-non-small-cell-lung-cancer
#18
Arnaud Jeanson, Fabrice Barlesi
Immune checkpoint inhibitors (ICI) are now a therapeutic option for advanced non-small cell lung cancer (NSCLC) patients. ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC. Other notable PD-L1 inhibitors under development include avelumab and durvalumab. Areas covered: This article reviews literature on durvalumab development, from the preclinical data to the results of phase III clinical trials, whether published or presented at international scientific conferences...
July 13, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28705007/pancreas-adenocarcinoma-novel-therapeutics
#19
Benjamin A Krantz, Kenneth H Yu, Eileen M O'Reilly
Pancreatic ductal adenocarcinoma (PDAC) is the third highest cause of cancer-related deaths in the US, and is projected to be second only to non-small cell lung cancer (NSCLC) by the 2020s. Current therapies have a modest impact on survival and median overall survival (mOS) across all stages of disease remains under a year. Over the last decade, however, great strides have been made in the understanding of PDAC pathobiology including the role of the tumor microenvironment (TME), DNA damage repair and mechanism of immunosuppression...
June 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28704840/hype-or-hope-the-prognostic-value-of-infiltrating-immune-cells-in-cancer
#20
Tristan A Barnes, Eitan Amir
Interactions between immune and malignant cells have been known to have clinical relevance for decades. The potential for immune control is now being therapeutically enhanced with checkpoint inhibitors and other novel agents to improve outcomes in cancer. The importance of the immune infiltrate as a prognostic marker is increasingly relevant. In this minireview, we present an overview of the immune infiltrate and its spatial organisation, and summarise the prognostic value of immune cells in different cancer types...
July 13, 2017: British Journal of Cancer
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