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Immuno checkpoint

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https://www.readbyqxmd.com/read/29428479/immuno-oncology-101-overview-of-major-concepts-and-translational-perspectives
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/29385739/precision-immuno-oncology-prospects-of-individualized-immunotherapy-for-pancreatic-cancer
#7
REVIEW
Jiajia Zhang, Christopher L Wolfgang, Lei Zheng
Pancreatic cancer, most commonly referring to pancreatic ductal adenocarcinoma (PDAC), remains one of the most deadly diseases, with very few effective therapies available. Emerging as a new modality of modern cancer treatments, immunotherapy has shown promises for various cancer types. Over the past decades, the potential of immunotherapy in eliciting clinical benefits in pancreatic cancer have also been extensively explored. It has been demonstrated in preclinical studies and early phase clinical trials that cancer vaccines were effective in eliciting anti-tumor immune response, but few have led to a significant improvement in survival...
January 30, 2018: Cancers
https://www.readbyqxmd.com/read/29375032/incorporating-radiation-oncology-into-immunotherapy-proceedings-from-the-astro-sitc-nci-immunotherapy-workshop
#8
Ariel E Marciscano, Joshua M Walker, Heather M McGee, Michelle M Kim, Charles A Kunos, Arta M Monjazeb, Stephen L Shiao, Phuoc T Tran, Mansoor M Ahmed
Radiotherapy (RT) has been a fundamental component of the anti-cancer armamentarium for over a century. Approximately half of all cancer patients are treated with radiotherapy during their disease course. Over the two past decades, there has been a growing body of preclinical evidence supporting the immunomodulatory effects of radiotherapy, particularly when combined with immunotherapy, but only anecdotal clinical examples existed until recently. The renaissance of immunotherapy and the recent U.S. Food and Drug Administration (FDA) approval of several immune checkpoint inhibitors (ICIs) and other immuno-oncology (IO) agents in multiple cancers provides the opportunity to investigate how localized radiotherapy can induce systemic immune responses...
January 29, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29350327/hypermutated-tumors-and-immune-checkpoint-inhibition
#9
Kristen K Ciombor, Richard M Goldberg
Microsatellite instability-high/DNA mismatch repair deficient tumors are found across the cancer spectrum and often harbor markedly increased numbers of mutations when compared to microsatellite stable/DNA mismatch repair proficient tumors. As a result of this high mutational load, tumor-infiltrating lymphocyte density is increased and more immunogenic neoepitopes are expressed, leading to upregulation of immune checkpoints in these tumors. Checkpoint inhibitors such as pembrolizumab and nivolumab, both immunoglobulin G4 (IgG4) monoclonal antibodies that block interactions between the programmed cell death receptor-1 and its ligands, have significant activity in this tumor class...
January 19, 2018: Drugs
https://www.readbyqxmd.com/read/29348318/response-optimizing-strategies-for-immune-checkpoint-imaging-with-immuno-pet-in-preclinical-study
#10
Aaron T Mayer, Sanjiv S Gambhir
No abstract text is available yet for this article.
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29332322/tumor-immunology-and-immune-checkpoint-inhibitors-in-non-small-cell-lung-cancer
#11
REVIEW
Chi Young Jung, Scott J Antonia
Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%-20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer...
January 2018: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29329113/therapeutic-hiv-1-vaccine-time-for-immunomodulation-and-combinatorial-strategies
#12
Nabila Seddiki, Yves Lévy
PURPOSE OF REVIEW: The purpose is to recall some of the key immunological elements that are at the crossroad and need to be combined for developing a potent therapeutic HIV-1 vaccine. RECENT FINDINGS: Therapeutic vaccines and cytokines have been commonly used to enhance and/or recall preexisting HIV-1 specific cell-mediated immune responses aiming to suppress virus replication. While the vaccine is important to stimulate HIV-1 specific T-cell responses, the cytokine may support the expansion of the stimulated virus-specific T cells...
January 10, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29311380/hitting-the-target-how-t-cells-detect-and-eliminate-tumors
#13
REVIEW
Anthony E Zamora, Jeremy Chase Crawford, Paul G Thomas
The successes of antitumor immuno-based therapies and the application of next-generation sequencing to mutation profiling have produced insights into the specific targets of antitumor T cells. Mutated proteins have tremendous potential as targets for interventions using autologous T cells or engineered cell therapies and may serve as important correlates of efficacy for immunoregulatory interventions including immune checkpoint blockade. As mutated self, tumors present an exceptional case for host immunity, which has primarily evolved in response to foreign pathogens...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29282151/the-changing-face-of-clinical-trials-in-the-personalized-medicine-and-immuno-oncology-era-report-from-the-international-congress-on-clinical-trials-in-oncology-hemato-oncology-icto-2017
#14
Talia Golan, Michele Milella, Aliza Ackerstein, Ranaan Berger
In the past decade, the oncology community has witnessed major advances in the understanding of cancer biology and major breakthroughs in several different therapeutic areas, from solid tumors to hematological malignancies; moreover, the advent of effective immunotherapy approaches, such as immune-checkpoint blockade, is revolutionizing treatment algorithms in almost all oncology disease areas. As knowledge evolves and new weapons emerge in the "war against cancer", clinical and translational research need to adapt to a rapidly changing environment to effectively translate novel concepts into sustainable and accessible therapeutic options for cancer patients...
December 28, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29212301/convergence-of-cancer-metabolism-and-immunity-an-overview
#15
REVIEW
Chi Van Dang, Jung-Whan Kim
Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells...
January 1, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29196189/pd-l1-inflammation-non-coding-rnas-and-neuroblastoma-immuno-oncology-perspective
#16
REVIEW
Palanisamy Nallasamy, Srinivas Chava, Sumit S Verma, Shruti Mishra, Santhi Gorantla, Don W Coulter, Siddappa N Byrareddy, Surinder K Batra, Subash C Gupta, Kishore B Challagundla
Neuroblastoma is the most common pediatric solid tumor of neural crest origin. The current treatment options for neuroblastoma produce severe side effects. Programmed death-ligand 1 (PD-L1), chronic inflammation, and non-coding RNAs are known to play a significant role in the pathogenesis of neuroblastoma. Cancer cells and the surrounding cells in the tumor microenvironment express PD-L1. Programmed death-1 (PD-1) is a co-receptor expressed predominantly by T cells. The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system...
November 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29170067/perspectives-on-the-integration-of-immuno-oncology-biomarkers-and-drugs-in-a-health-care-setting
#17
REVIEW
K Vermaelen, A Waeytens, O Kholmanskikh, M Van den Bulcke, E Van Valckenborgh
Immunotherapies, specifically checkpoint inhibitors, are becoming an important component in cancer care with the most application now in melanoma and lung cancer patients. Some drawbacks that converge with this new evolution are the rather low response rates to these drugs and their high cost with a significant economic impact on the health care system. These major challenges can likely be circumvented by implementing a "personalized immuno-oncology" approach to accomplish a selection of optimal responders based on biomarkers...
November 20, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29155348/progress-and-challenges-of-predictive-biomarkers-of-anti-pd-1-pd-l1-immunotherapy-a-systematic-review
#18
Feifei Teng, Xiangjiao Meng, Li Kong, Jinming Yu
Despite the marked success of applications of PD-1/PD-L1 checkpoint blockades in clinical, the efficacy and responsiveness of these agents varies greatly among different tumor types and across individual patients. Therefore, establishment of predictive biomarkers for checkpoint blockades is of the most importance to maximize the therapeutic benefits. In this review, we discuss the current progress and challenges of developing predictive biomarkers of immunotherapy responsiveness, aiming to provide some directions for future studies...
February 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29147618/programmed-cell-death-ligands-expression-in-phaeochromocytomas-and-paragangliomas-relationship-with-the-hypoxic-response-immune-evasion-and-malignant-behavior
#19
David J Pinato, James R Black, Sebastian Trousil, Roberto E Dina, Pritesh Trivedi, Francesco A Mauri, Rohini Sharma
The hypoxic response underlies the pathogenesis and malignant behavior of PCC/PGL. Regulation of PD-1 receptor-ligand signaling, a therapeutically actionable driver of the anti-tumor immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 and 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29141914/proteotranscriptomics-reveal-signaling-networks-in-the-ovarian-cancer-microenvironment
#20
Thomas Worzfeld, Florian Finkernagel, Silke Reinartz, Anne Konzer, Till Adhikary, Andrea Nist, Thorsten Stiewe, Uwe Wagner, Mario Looso, Johannes Graumann, Rolf Müller
Ovarian cancer is characterized by early transcoelomic metastatic spread via the peritoneal fluid, where tumor cell spheroids (TU), tumor-associated T cells (TAT), and macrophages (TAM) create a unique microenvironment promoting cancer progression, chemoresistance and immuno-suppression. However, the underlying signaling mechanisms remain largely obscure.  To chart these signaling networks, we performed comprehensive proteomic and transcriptomic analyses of TU, TAT and TAM from ascites of ovarian cancer patients...
November 15, 2017: Molecular & Cellular Proteomics: MCP
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