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Immuno checkpoint

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https://www.readbyqxmd.com/read/29670099/nuclear-receptor-nr2f6-inhibition-potentiates-responses-to-pd-l1-pd-1-cancer-immune-checkpoint-blockade
#1
Victoria Klepsch, Natascha Hermann-Kleiter, Patricia Do-Dinh, Bojana Jakic, Anne Offermann, Mirjana Efremova, Sieghart Sopper, Dietmar Rieder, Anne Krogsdam, Gabriele Gamerith, Sven Perner, Alexandar Tzankov, Zlatko Trajanoski, Dominik Wolf, Gottfried Baier
Analyzing mouse tumor models in vivo, human T cells ex vivo, and human lung cancer samples, we provide direct evidence that NR2F6 acts as an immune checkpoint. Genetic ablation of Nr2f6, particularly in combination with established cancer immune checkpoint blockade, efficiently delays tumor progression and improves survival in experimental mouse models. The target genes deregulated in intratumoral T lymphocytes upon genetic ablation of Nr2f6 alone or together with PD-L1 blockade reveal multiple advantageous transcriptional alterations...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29629216/novel-systemic-therapies-for-advanced-gastric-cancer
#2
REVIEW
Hong Jun Kim, Sang Cheul Oh
Gastric cancer (GC) is the second leading cause of cancer mortality and the fourth most commonly diagnosed malignant diseases. While continued efforts have been focused on GC treatment, the introduction of trastuzumab marked the beginning of a new era of target-specific treatments. Considering the diversity of mutations in GC, satisfactory results obtained from various target-specific therapies were expected, yet most of them were unsuccessful in controlled clinical trials. There are several possible reasons underlying the failures, including the absence of patient selection depending on validated predictive biomarkers, the inappropriate combination of drugs, and tumor heterogeneity...
March 2018: Journal of Gastric Cancer
https://www.readbyqxmd.com/read/29587322/-the-role-of-biomarkers-in-the-diagnosis-prognosis-and-therapy-of-patients-with-immuno-oncological-treatments-of-genito-urinary-carcinomas
#3
Eva Compérat, Caroline Eymerit, Julien Moroch, Justin Varinot
In recent years, fundamental research has yielded new insights into tumour biology, and new treatments have been developed. This review highlights the role of the pathologist and how he can support clinicians to find the right treatment for each patient. We explain the problems of the molecular subgroups of bladder cancer, the role of neo-adjuvant chemotherapy in the context of these findings, and show the important role of checkpoint inhibitors. Furthermore we focus on kidney cancer, with the clear cell carcinoma as the most frequent tumour type...
April 2018: Aktuelle Urologie
https://www.readbyqxmd.com/read/29581255/anti-ctla-4-therapy-requires-an-fc-domain-for-efficacy
#4
Jessica R Ingram, Olga S Blomberg, Mohammad Rashidian, Lestat Ali, Scott Garforth, Elena Fedorov, Alexander A Fedorov, Jeffrey B Bonanno, Camille Le Gall, Stephanie Crowley, Camilo Espinosa, Tamara Biary, Edmund J Keliher, Ralph Weissleder, Steven C Almo, Stephanie K Dougan, Hidde L Ploegh, Michael Dougan
Ipilimumab, a monoclonal antibody that recognizes cytotoxic T lymphocyte antigen (CTLA)-4, was the first approved "checkpoint"-blocking anticancer therapy. In mouse tumor models, the response to antibodies against CTLA-4 depends entirely on expression of the Fcγ receptor (FcγR), which may facilitate antibody-dependent cellular phagocytosis, but the contribution of simple CTLA-4 blockade remains unknown. To understand the role of CTLA-4 blockade in the complete absence of Fc-dependent functions, we developed H11, a high-affinity alpaca heavy chain-only antibody fragment (VHH) against CTLA-4...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29567211/cardiac-toxicity-in-patients-treated-with-immune-checkpoint-inhibitors-it-is-now-time-for-cardio-immuno-oncology
#5
EDITORIAL
Carlo G Tocchetti, Maria Rosaria Galdiero, Gilda Varricchi
No abstract text is available yet for this article.
March 13, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29565054/-metastatic-lung-adenocarcinoma-nivolumab-as-second-line-treatment-between-unresolved-issues-and-promising-future-a-case-report
#6
Diego Luigi Cortinovis
In recent years immunotherapy has become a fundamental part of the treatment of many solid tumors, including non-small cell lung cancer (NSCLC). With the results of trials investigating the role of monoclonal antibodies against immuno-checkpoints in particular, today these drugs have become part of everyday clinical practice, even though many questions still remain unresolved (optimal duration of treatment, prognostic and predictive role of biomarkers, management of immuno-related toxicity). Here we report the case of our patient with diagnosis of metastatic lung adenocarcinoma "non oncogene driven" successfully treated in second line with nivolumab, analyzing the problems and the questions most frequently evidenced during treatment with these new molecules...
March 2018: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/29530602/drug-induced-xenogenization-of-tumors-a-possible-role-in-the-immune-control-of-malignant-cell-growth-in-the-brain
#7
REVIEW
Ornella Franzese, Fiorenzo Battaini, Grazia Graziani, Lucio Tentori, Maria Luisa Barbaccia, Angelo Aquino, Mario Roselli, Maria Pia Fuggetta, Enzo Bonmassar, Francesco Torino
In recent years, immune checkpoint inhibitors (ICpI) have provided the ground to bring tumor immunity back to life thanks to their capacity to afford a real clinical benefit in terms of patient's survival. Essential to ICpI success is the presence of tumor-associated neoantigens generated by non-synonymous mutations, since a direct relationship between mutation load of malignant cells and susceptibility to ICpI has been confidently established. However, it has been also suggested that high intratumor heterogeneity (ITH) associated with subclonal neoantigens could not elicit adequate immune responses...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29524617/state-of-the-art-advances-in-malignant-pleural-mesothelioma-in-2017
#8
REVIEW
Amanda J McCambridge, Andrea Napolitano, Aaron S Mansfield, Dean A Fennell, Yoshitaka Sekido, Anna K Nowak, Thanyanan Reungwetwattana, Weimin Mao, Harvey I Pass, Michele Carbone, Haining Yang, Tobias Peikert
Malignant pleural mesothelioma (MPM) is an uncommon, almost universally fatal, asbestos-induced malignancy. New and effective strategies for diagnosis, prognostication and treatment are urgently needed. Herein we review the advances in MPM achieved in 2017. While recent epidemiological data demonstrated that the incidence of MPM-related death continued to increase in United States between 2009 and 2015, new insight into the molecular pathogenesis and the immunological tumor microenvironment of MPM, for example, regarding the role of BRCA1 associated protein 1 (BAP1) and the expression programmed death receptor ligand 1 (PD-L1), are highlighting new potential therapeutic strategies...
March 7, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29520448/targeting-the-tumor-microenvironment-with-immunotherapy-for-genitourinary-malignancies
#9
REVIEW
Ariel E Marciscano, Ravi A Madan
Bacillus Calmette-Guérin in urothelial carcinoma, high-dose interleukin-2 in renal cell carcinoma, and sipuleucel-T in prostate cancer serve as enduring examples that the host immune response can be harnessed to promote effective anti-tumor immunity in genitourinary malignancies. Recently, cancer immunotherapy with immune checkpoint inhibitors has transformed the prognostic landscape leading to durable responses in a subset of urothelial carcinoma and renal cell carcinoma patients with traditionally poor prognosis...
March 8, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29514782/the-myc-oncogene-is-a-global-regulator-of-the-immune-response
#10
Stephanie C Casey, Virginie Baylot, Dean W Felsher
The MYC proto-oncogene is a gene product that coordinates the transcriptional regulation of a multitude of genes that are essential to cellular programs required for normal as well as neoplastic cellular growth and proliferation, including cell cycle, self-renewal, survival, cell growth, metabolism, protein and ribosomal biogenesis, and differentiation. Here we propose that MYC regulates these programs in a manner that is coordinated with a global influence on the host immune response. MYC had been presumed to contribute to tumorigenesis through tumor cell intrinsic influences...
March 7, 2018: Blood
https://www.readbyqxmd.com/read/29507655/immune-checkpoint-inhibitors-in-neuroendocrine-tumors-a-single-institution-experience-with-review-of-literature
#11
Aman Chauhan, Millicent Horn, Gray Magee, Kurt Hodges, Mark Evers, Susanne Arnold, Lowell Anthony
This unique case series and review of literature suggests that immune checkpoint inhibitors may have clinical activity in neuroendocrine tumors. Objective: Summarize advances of immuno-oncology in neuroendocrine tumors with the help of a case series. Design: Case series and review of literature. Intervention or Exposure: The patients were treated with immune checkpoint inhibitors (pembrolizumab or nivolumab). Main Outcomes and Measuress: Life expectancy, quality of life, disease progression...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29502426/immuno-pet-imaging-of-89zr-labeled-anti-pd-l1-domain-antibody
#12
Dan Li, Siyuan Cheng, Sijuan Zou, Dongling Zhu, Tinghui Zhu, Pilin Wang, Xiaohua Zhu
Recently, various immuno-PET tracers based on monoclonal antibodies (mAbs), engineered scaffold proteins and peptides were developed to target either programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1), showing promise in assessment of immune checkpoints. We sought to develop an immunotherapeutic agent-based PET probe that enable real-time assessment of PD-L1 expression and evaluation of antibody drug biodistribution to select eligible candidates for anti-PD-1/PD-L1 immunotherapies...
March 5, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29463044/the-role-of-the-estrogen-pathway-in-the-tumor-microenvironment
#13
REVIEW
Natalie J Rothenberger, Ashwin Somasundaram, Laura P Stabile
Estrogen receptors are broadly expressed in many cell types involved in the innate and adaptive immune responses, and differentially regulate the production of cytokines. While both genomic and non-genomic tumor cell promoting mechanisms of estrogen signaling are well characterized in multiple carcinomas including breast, ovarian, and lung, recent investigations have identified a potential immune regulatory role of estrogens in the tumor microenvironment. Tumor immune tolerance is a well-established mediator of oncogenesis, with increasing evidence indicating the importance of the immune response in tumor progression...
February 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29460015/-immuno-radio-and-chemotherapeutic-studies-in-head-and-neck-cancer-highlights-of-the-asco-annual-meeting-2017
#14
REVIEW
P J Schuler, A von Witzleben, J Doescher, B Wollenberg, A Dietz, T K Hoffmann
In recent years, immunotherapy has been shown to be a promising approach for the treatment of various tumor entities. Due to further pharmacological developments and new studies, the checkpoint inhibitors have now arrived in the clinic. To date, patients with cancers in the head and neck region have benefited from these agents as part of a palliative therapy. Current clinical trials are testing other indications for the checkpoint inhibitors as monotherapy or in combination with other therapeutic approaches...
February 19, 2018: HNO
https://www.readbyqxmd.com/read/29428479/immuno-oncology-101-overview-of-major-concepts-and-translational-perspectives
#15
REVIEW
B Allard, S Aspeslagh, S Garaud, F A Dupont, C Solinas, M Kok, B Routy, C Sotiriou, J Stagg, L Buisseret
Cancer immunotherapy is demonstrating impressive clinical benefit in different malignancies and clinical oncologists are increasingly turning their attention to immune-oncology. It is now well recognized that innate and adaptive immune cells infiltrating tumors are associated with clinical outcomes and responses to treatments, and can be harnessed to patients' benefit. Considerable advances have also been made in understanding how cancers escape from immune attack. Targeting of immunological escape processes regulated by the expression of immune checkpoint receptors and ligands and the down-modulation of tumor antigen presentation is the basis of immuno-oncology treatments...
February 8, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29417397/cancer-immunotherapy-factors-important-for-the-evaluation-of-safety-in-nonclinical-studies
#16
Danuta J Herzyk, Helen G Haggerty
The development of novel therapies that can harnass the immune system to eradicate cancer is an area of intensive research. Several new biopharmaceuticals that target the immune system rather than the tumor itself have recently been approved and fundamentally transformed treatment of many cancer diseases. This success has intensified the search for new targets and modalities that could be developed as even more effective therapeutic agents either as monotherapy or in combination. While great benefits of novel immunotherapies in oncology are evident, the safety of these therapies has to also be addressed as their desired pharmacology, immune activation, can lead to "exaggerated" effects and toxicity...
February 7, 2018: AAPS Journal
https://www.readbyqxmd.com/read/29415055/tissue-analyses-reveal-a-potential-immune-adjuvant-function-of-fap-1-positive-fibroblasts-in-non-small-cell-lung-cancer
#17
Thomas Karsten Kilvaer, Mehrdad Rakaee, Turid Hellevik, Arne Østman, Carina Strell, Roy M Bremnes, Lill-Tove Busund, Tom Dønnem, Inigo Martinez-Zubiaurre
OBJECTIVES: Selective targeting of cancer-associated fibroblasts (CAFs) has been proposed to synergize with immune-checkpoint inhibitors. While the roles of CAFs in cancer development are well described, their immune-regulatory properties remain incompletely understood. This study investigates correlations between CAF and immune-markers in tumor stroma from non-small cell lung cancer (NSCLC) patients, and examines whether a combination of CAF and immune cell scores impact patient prognosis...
2018: PloS One
https://www.readbyqxmd.com/read/29405579/a-cisplatin-loaded-immuno-chemotherapeutic-nanohybrid-bearing-immune-checkpoint-inhibitors-for-enhanced-cervical-cancer-therapy
#18
Na Wang, Zhigang Wang, Zoufeng Xu, Xianfeng Chen, Guangyu Zhu
The efficacy of conventional chemotherapy is hindered by cancer cells' escape from the immune system. Herein, we report a multifunctional nanohybrid system for effective immuno-chemotherapy against cervical cancer. This nanohybrid contains both immune checkpoint inhibitor and cisplatin anticancer prodrug, showing improved cellular accumulation and increased binding of Pt to DNA and resulting in elevated apoptosis than using cisplatin alone when tested in cervical cancer cells. Intriguingly, the use of immune checkpoint inhibitors enables the inhibition of indoleamine-2,3-dioxygenase and reverses immunosuppressive T cells to recognize cancer cells, leading to T cell proliferation and activation, cancer cell cycle arrest, and ultimately increased cancer cell death...
February 5, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29399441/nk-cells-and-%C3%AE-%C3%AE-t-cells-for-relapse-protection-after-allogeneic-hematopoietic-cell-transplantation-hct
#19
Moniek A de Witte, Jürgen Kuball, Jeffrey S Miller
Purpose of review: The outcome of allogeneic stem cell transplantation (allo-HCT) is still compromised by relapse and complications. NK cells and γδT cells, effectors which both function through MHC-unrestricted mechanisms, can target transformed and infected cells without inducing Graft-versus-Host Disease (GVHD). Allo-HCT platforms based on CD34+ selection or αβ-TCR depletion result in low grades of GVHD, early immune reconstitution (IR) of NK and γδT cells and minimal usage of GVHD prophylaxis...
December 2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/29399401/a-safe-and-highly-efficient-tumor-targeted-type-i-interferon-immunotherapy-depends-on-the-tumor-microenvironment
#20
Anje Cauwels, Sandra Van Lint, Geneviève Garcin, Jennyfer Bultinck, Franciane Paul, Sarah Gerlo, José Van der Heyden, Yann Bordat, Dominiek Catteeuw, Lode De Cauwer, Elke Rogge, Annick Verhee, Gilles Uzé, Jan Tavernier
Despite approval for the treatment of various malignancies, clinical application of cytokines such as type I interferon (IFN) is severely impeded by their systemic toxicity. AcTakines (Activity-on-Target cytokines) are optimized immunocytokines that, when injected in mice, only reveal their activity upon cell-specific impact. We here show that type I IFN-derived AcTaferon targeted to the tumor displays strong antitumor activity without any associated toxicity, in contrast with wild type IFN. Treatment with CD20-targeted AcTaferon of CD20+ lymphoma tumors or melanoma tumors engineered to be CD20+, drastically reduced tumor growth...
2018: Oncoimmunology
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