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https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#1
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28324153/epigenetics-in-the-pathogenesis-of-ra
#2
REVIEW
Caroline Ospelt, Steffen Gay, Kerstin Klein
Epigenetic modifications can stably alter gene expression and have been shown to be important in the maintenance of cell type-specific functions as well as in cell differentiation, e.g., in T and B cell maturation. In RA, alterations in DNA methylation, histone modifications, and microRNA expression have been found in immune as well as in stromal cells. These changes in the epigenome in RA patients influence key inflammatory and matrix-degrading pathways and are suspected to play a major role in the pathogenesis of RA...
March 21, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28323646/endothelial-cells-and-lymphatics-at-the-interface-between-the-immune-and-central-nervous-systems-implications-for-multiple-sclerosis
#3
Céline Meyer, Guillaume Martin-Blondel, Roland S Liblau
PURPOSE OF REVIEW: The central nervous system (CNS) has a unique relationship with the immune system. This review highlights the distinct roles of lymphatic vessels and endothelial cells in the interface between CNS and immune cells and invites to revisit the concept of CNS immune privilege. RECENT FINDINGS: T cells can follow several routes to penetrate the CNS parenchyma but may also benefit, together with antigen-loaded presenting cells, from the newly described lymphatic network to exit the CNS...
March 18, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28323492/regulatory-and-exhausted-t-cell-responses-to-aav-capsid
#4
Gwladys Gernoux, James M Wilson, Christian Mueller
Recombinant adeno-associated viruses are quickly becoming the preferred viral vector for viral gene delivery for the treatment of a wide variety of genetic disorders. However, since their use in a clinical trial targeting Hemophilia B patients 10 years ago, immune responses to AAV capsid appear to have hampered some of the early clinical gene transfer efficacy. Indeed, AAV-based gene transfer has been shown to reactivate capsid-specific memory T cells which have correlated with a decline in AAV transduced tissue in some patients...
March 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28319073/ex-vivo-t-cell-depletion-in-allogeneic-hematopoietic-stem-cell-transplant-past-present-and-future
#5
REVIEW
A Saad, L S Lamb
The most common cause of post-transplant mortality in patients with hematological malignancy is relapse, followed by GvHD, infections, organ toxicity and second malignancy. Immune-mediated complications such as GvHD continue to be challenging, yet amenable to control through manipulation of the T-cell compartment of the donor graft with subsequent immunomodulation after transplant. However, risk of both relapse and infection increase concomitantly with T-cell depletion (TCD) strategies that impair immune recovery...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28318492/-brain-tumor-immunotherapy-illusion-or-hope
#6
REVIEW
Denis Migliorini, Valérie Dutoit, Paul R Walker, Pierre-Yves Dietrich
Immunotherapy has proven efficient for many tumors and is now part of standard of care in many indications. What is the picture for brain tumors? The recent development of anti-CTLA-4 and PD1 immune checkpoint inhibitors, which have the ability to restore T lymphocytes activity, has gathered enthusiasm and is now paving the way towards more complex models of immune system manipulation. These models include, among others, vaccination and adoptive T cell transfer technologies. Complementary to those strategies, molecules capable of reshaping the immune tumor microenvironment are currently being investigated in early phase trials...
March 16, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28317923/generation-of-diversity-in-thymic-epithelial-cells
#7
REVIEW
Yousuke Takahama, Izumi Ohigashi, Song Baik, Graham Anderson
In the thymus, diverse populations of thymic epithelial cells (TECs), including cortical and medullary TECs and their subpopulations, have distinct roles in coordinating the development and repertoire selection of functionally competent and self-tolerant T cells. Here, we review the expanding diversity in TEC subpopulations in relation to their functions in T cell development and selection as well as their origins and development.
March 20, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28317871/insights-into-molecular-therapy-of-glioma-current-challenges-and-next-generation-blueprint
#8
REVIEW
Y Rajesh, Ipsita Pal, Payel Banik, Sandipan Chakraborty, Sachin A Borkar, Goutam Dey, Ahona Mukherjee, Mahitosh Mandal
Glioma accounts for the majority of human brain tumors. With prevailing treatment regimens, the patients have poor survival rates. In spite of current development in mainstream glioma therapy, a cure for glioma appears to be out of reach. The infiltrative nature of glioma and acquired resistance substancially restrict the therapeutic options. Better elucidation of the complicated pathobiology of glioma and proteogenomic characterization might eventually open novel avenues for the design of more sophisticated and effective combination regimens...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28317239/the-use-of-low-dose-metronomic-chemotherapy-in-dogs-insight-into-a-modern-cancer-field
#9
REVIEW
T B Gaspar, J Henriques, L Marconato, F L Queiroga
The era of chemotherapy, which started in the middle of the last century, has been ruled by the routine use of dose-intense protocols, based on the "maximum-tolerated dose" concept. By promoting a balance between patient's quality of life and the goal of rapidly killing as many tumour cells as possible, these protocols still play a prominent role in veterinary oncology. However, with the opening of a new millennium, metronomic chemotherapy (MC) started to be considered a possible alternative to traditional dose-intense chemotherapy...
March 20, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28316998/il-10-a-multifunctional-cytokine-in-viral-infections
#10
REVIEW
José M Rojas, Miguel Avia, Verónica Martín, Noemí Sevilla
The anti-inflammatory master regulator IL-10 is critical to protect the host from tissue damage during acute phases of immune responses. This regulatory mechanism, central to T cell homeostasis, can be hijacked by viruses to evade immunity. IL-10 can be produced by virtually all immune cells, and it can also modulate the function of these cells. Understanding the effects of this multifunctional cytokine is therefore a complex task. In the present review we discuss the factors driving IL-10 production and the cellular sources of the cytokine during antiviral immune responses...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28316997/sildenafil-can-affect-innate-and-adaptive-immune-system-in-both-experimental-animals-and-patients
#11
REVIEW
Monika Kniotek, Agnieszka Boguska
Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I), is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is) found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28316374/the-role-of-il-17-and-related-cytokines-in-inflammatory-autoimmune-diseases
#12
REVIEW
Taku Kuwabara, Fumio Ishikawa, Motonari Kondo, Terutaka Kakiuchi
Interleukin-17 (IL-17) induces the production of granulocyte colony-stimulating factor (G-CSF) and chemokines such as CXCL1 and CXCL2 and is a cytokine that acts as an inflammation mediator. During infection, IL-17 is needed to eliminate extracellular bacteria and fungi, by inducing antimicrobial peptides such as defensin. This cytokine also plays an important role in chronic inflammation that occurs during the pathogenesis of autoimmune diseases and allergies such as human rheumatoid arthritis (RA) for which a mouse model of collagen-induced arthritis (CIA) is available...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28315224/an-overview-of-bioinformatics-tools-and-resources-in-allergy
#13
Zhiyan Fu, Jing Lin
The rapidly increasing number of characterized allergens has created huge demands for advanced information storage, retrieval, and analysis. Bioinformatics and machine learning approaches provide useful tools for the study of allergens and epitopes prediction, which greatly complement traditional laboratory techniques. The specific applications mainly include identification of B- and T-cell epitopes, and assessment of allergenicity and cross-reactivity. In order to facilitate the work of clinical and basic researchers who are not familiar with bioinformatics, we review in this chapter the most important databases, bioinformatic tools, and methods with relevance to the study of allergens...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28314253/the-role-of-il-7-in-immunity-and-cancer
#14
REVIEW
Jack Lin, Ziwen Zhu, Huaping Xiao, Mark R Wakefield, Vivi A Ding, Qian Bai, Yujiang Fang
Interleukin-7 (IL-7) is a cytokine that has been known since long in immunology, mainly regarding its effects on T-cells and B-cells. IL-7 has been demonstrated to be necessary for both B-cell and T-cell proliferation and lack of IL-7 causes immature immune cell arrest. Interestingly, in recent years, certain studies have strongly suggested that the role of IL-7 is far beyond the field of immunology, it might have direct or indirect effect on cancer. This review aims to summarize the role of IL-7 in immunity and its role in the pathogenesis of neoplasia...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28306601/assessing-the-impact-of-diabetes-mellitus-on-donor-corneal-endothelial-cell-density
#15
Chase A Liaboe, Benjamin T Aldrich, Pamela C Carter, Jessica M Skeie, Kimberlee A Burckart, Gregory A Schmidt, Cynthia R Reed, M Bridget Zimmerman, Mark A Greiner
PURPOSE: To quantify changes in endothelial cell density (ECD) of donor corneal tissue in relation to the presence or absence of a medical history of diabetes mellitus diagnosis, treatment, and complications. METHODS: A retrospective review was performed for all corneas collected at Iowa Lions Eye Bank between January 2012 and December 2015. For purposes of analysis, donor corneas were divided into 4 groups: nondiabetic, non-insulin-dependent diabetic, insulin-dependent diabetic without medical complications due to diabetes, and insulin-dependent diabetic with medical complications due to diabetes...
March 16, 2017: Cornea
https://www.readbyqxmd.com/read/28304347/plausible-roles-for-rage-in-conditions-exacerbated-by-direct-and-indirect-secondhand-smoke-exposure
#16
REVIEW
Joshua B Lewis, Kelsey M Hirschi, Juan A Arroyo, Benjamin T Bikman, David L Kooyman, Paul R Reynolds
Approximately 1 billion people smoke worldwide, and the burden placed on society by primary and secondhand smokers is expected to increase. Smoking is the leading risk factor for myriad health complications stemming from diverse pathogenic programs. First- and second-hand cigarette smoke contains thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic inflammatory responses and destructive remodeling events. In the current review, we outline details related to compromised pulmonary and systemic conditions related to smoke exposure...
March 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28304339/the-five-immune-forces-impacting-dna-based-cancer-immunotherapeutic-strategy
#17
REVIEW
Suneetha Amara, Venkataswarup Tiriveedhi
DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success...
March 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28304115/extracorporeal-photopheresis-in-pediatric-patients-practical-and-technical-considerations
#18
Robert A DeSimone, Joseph Schwartz, Jennifer Schneiderman
In adults, extracorporeal photopheresis (ECP) is widely utilized for a variety of indications, most commonly cutaneous T-cell lymphoma, acute or chronic graft-versus-host disease (GVHD), solid organ transplant rejection, and other autoimmune and T-cell-mediated disorders. In pediatric patients, the majority of case series and reports have focused on its use in the management of acute and chronic GVHD. Currently utilized ECP technologies were designed for adult patients and there are several challenges in adapting these technologies for use in children...
March 17, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28303905/pre-metastatic-niches-organ-specific-homes-for-metastases
#19
REVIEW
Héctor Peinado, Haiying Zhang, Irina R Matei, Bruno Costa-Silva, Ayuko Hoshino, Goncalo Rodrigues, Bethan Psaila, Rosandra N Kaplan, Jacqueline F Bromberg, Yibin Kang, Mina J Bissell, Thomas R Cox, Amato J Giaccia, Janine T Erler, Sachie Hiratsuka, Cyrus M Ghajar, David Lyden
It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche...
March 17, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28303782/paradoxical-reactions-and-the-immune-reconstitution-inflammatory-syndrome
#20
L W Preston Church, Amit Chopra, Marc A Judson
In HIV-infected individuals, paradoxical reactions after the initiation of antiretroviral therapy (ART) are associated with a variety of underlying infections and have been called the immune reconstitution inflammatory syndrome (IRIS). In cases of IRIS associated with tuberculosis (TB), two distinct patterns of disease are recognized: (i) the progression of subclinical TB to clinical disease after the initiation of ART, referred to as unmasking, and (ii) the progression or appearance of new clinical and/or radiographic disease in patients with previously recognized TB after the initiation of ART, the classic or "paradoxical" TB-IRIS...
March 2017: Microbiology Spectrum
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