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https://www.readbyqxmd.com/read/28545032/endoplasmic-reticulum-stress-mediated-membrane-expression-of-crt-erp57-induces-immunogenic-apoptosis-in-drug-resistant-endometrial-cancer-cells
#1
Qin Xu, Chuanben Chen, An Lin, Yunqing Xie
OBJECTIVE: To investigate the role of endoplasmic reticulum (ER) stress-mediated CRT/ERp57 complex expression underlying the mechanism of resistance to doxorubicin (DOX) in endometrial carcinoma (EC) in vivo and in vitro. METHODS: The expression of CRT, ERp57, p-PERK, eIF2α, p-eIF2α in EC patients and EC cells was detected by Western blots and by immunofluorescence assay. MTT assay was used to determine the LC50 of EC cells to DOX and cell viability. Apoptosis was assayed using flow cytometer...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544973/pegylation-of-a-tlr2-agonist-based-vaccine-delivery-system-improves-antigen-trafficking-and-the-magnitude-of-ensuing-antibody-and-cd8-t-cell-responses
#2
Toshiki Sekiya, Junya Yamagishi, John Henry V Gray, Paul G Whitney, Axel Martinelli, Weiguang Zeng, Chinn Yi Wong, Chihiro Sugimoto, David C Jackson, Brendon Y Chua
The lipopeptide R4Pam2Cys is an agonist for toll-like receptor-2 (TLR2), a key pathogen-associated molecular pattern receptor expressed on many antigen-presenting cells such as dendritic cells (DCs). Electrostatic association of R4Pam2Cys with soluble protein antigens significantly enhances their immunogenicity and there is evidence to suggest that reducing the size of suitably adjuvanted-antigen complexes in solution may further improve their immunostimulatory capabilities. In this study, we investigated how incorporation of polyethylene glycol (PEG) into R4Pam2Cys affects the size, activity and efficacy of formed antigen-lipopeptide complexes...
May 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28544686/regulatory-t-cells-and-ctla-4-in-idiopathic-nephrotic-syndrome
#3
Shoji Tsuji, Takahisa Kimata, Sohsaku Yamanouchi, Tetsuya Kitao, Jiro Kino, Chikushi Suruda, Kazunari Kaneko
The pathogenesis of idiopathic nephrotic syndrome (INS) remains unknown. Recently, it was postulated that suppression of regulatory T cells (Treg) leads to massive proteinuria in INS, although there is some controversy. Considering the important role of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in Treg-mediated immune suppression, the aim of this study was therefore to clarify the involvement of Treg and CTLA-4 in the pathogenesis of INS. Fifteen patients with INS were enrolled. Their blood was sampled twice, once at onset and once at remission induced by glucocorticoid...
May 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28544604/thymic-peripheral-crosstalk-in-lymphodepletion-therapy
#4
EDITORIAL
M E Snyder, D L Farber
T cell depletion is widely used as induction therapy in solid organ transplants and particularly in kidney transplantation, to reduce the episodes of acute cellular rejection. The resultant reduction in T cell numbers is usually temporary, as T cells are actively replenished due to thymic output and/or lymphopenia-induced proliferation of remaining, depletion-resistant T cells. However, the extent of T cell replenishment and the persistence of lymphopenia varies between individuals, with potential impacts on protective or pathogenic immune responses...
May 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28544595/severe-cytokine-release-syndrome-in-a-patient-receiving-pd-1-directed-therapy
#5
Seth J Rotz, Daniel Leino, Sara Szabo, Jennifer L Mangino, Brian K Turpin, Joseph G Pressey
Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors is an approach to antitumor immune system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment with anti-PD-1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin-6 inhibitor tocilizumab and corticosteroids...
May 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28544545/cytoprotective-encapsulation-of-individual-jurkat-t-cells-within-durable-tio2-shells-for-t-cell-therapy
#6
Wongu Youn, Eun Hyea Ko, Mi-Hee Kim, Matthew Park, Daewha Hong, Gulaim A Seisenbaeva, Vadim G Kessler, Insung S Choi
Lymphocytes, such as T cells and natural killer (NK) cells, have therapeutic promises in adoptive cell transfer (ACT) therapy, where the cells are activated and expanded in vitro, and then infused into a patient. However, the in vitro preservation of labile lymphocytes during transfer, manipulation, and storage has been one of the bottlenecks in the development and commercialization of therapeutic lymphocytes. Herein, we suggest a "cell-in-shell" (a.k.a. artificial spore) strategy to enhance the cell viability in the practical settings, while maintaining biological activities for therapeutic efficacy...
May 25, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28544542/conditional-macrophage-depletion-increases-inflammation-and-does-not-inhibit-the-development-of-osteoarthritis-in-obese-mafia-mice
#7
Chia-Lung Wu, Jenna McNeill, Kelsey Goon, Dianne Little, Kelly Kimmerling, Janet Huebner, Virginia Kraus, Farshid Guilak
OBJECTIVE: Macrophages are believed to play a critical role in the inflammation associated with the development of osteoarthritis (OA) in obesity. The objective of the study was to investigate whether short-term, systemic depletion of macrophages would mitigate OA following injury in obese mice. METHODS: CSF-1R-GFP(+) Macrophage Fas-Induced Apoptosis (MaFIA) transgenic mice that allow conditional depletion of macrophages were placed on a high-fat diet and underwent surgery to induce knee OA...
May 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28544524/increase-of-cells-expressing-pd-1-and-pd-l1-and-enhancement-of-ifn-%C3%AE-production-via-pd-1-pd-l1-blockade-in-bovine-mycoplasmosis
#8
Shinya Goto, Satoru Konnai, Tomohiro Okagawa, Asami Nishimori, Naoya Maekawa, Satoshi Gondaira, Hidetoshi Higuchi, Masateru Koiwa, Motoshi Tajima, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
INTRODUCTION: Bovine mycoplasma, chiefly Mycoplasma bovis, is a pathogen that causes pneumonia, mastitis, arthritis, and otitis media in cattle. This pathogen exerts immunosuppressive effects, such as the inhibition of interferon production. However, the mechanisms involved in bovine mycoplasmosis have not been fully elucidated. In this study, we investigated the role of the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in immunosuppression in bovine mycoplasmosis...
May 24, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28544366/enumeration-of-wt1-specific-cd8-t-cells-for-clinical-application-using-an-mhc-streptamer-based-no-wash-single-platform-flow-cytometric-assay
#9
Sarah Matko, Madeleine Teichert, Antje Tunger, Marc Schmitz, Martin Bornhauser, Torsten Tonn, Marcus Odendahl
The advent of novel strategies to generate leukemia-associated-antigen (LAA)-specific T cells for adoptive immunotherapies creates a demand for standardized good laboratory practice (GLP)-compliant enumeration assays to provide a secure clinical environment-whether it is to identify potential donors, define therapeutic doses for transplantation, or monitor clinical success. Here, we introduce a no-wash assay based on single-platform cell enumeration and Streptamer staining to determine the Wilms' tumor antigen 1 (WT1)-specific T cell immunity in clinical samples...
May 25, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28544264/ampk-%C3%AE-1-reduces-tumor-progression-and-improves-survival-in-p53-null-mice
#10
Vanessa P Houde, Sara Donzelli, Andrea Sacconi, Sandra Galic, Joanne A Hammill, Jonathan L Bramson, Robert A Foster, Theodoros Tsakiridis, Bruce E Kemp, Giuseppe Grasso, Giovanni Blandino, Paola Muti, Gregory R Steinberg
The AMP-activated protein kinase (AMPK) is a heterotrimeric protein complex that is an important sensor of cellular energy status. Reduced expression of the AMPK β1 isoform has been linked to reduced survival in different cancers but whether this accelerates tumor progression and the potential mechanism mediating these effects is not known. Further, it is unknown whether AMPK β1 is implicated in tumorigenesis and if so what tissues may be most sensitive. In the current study we find that in the absence of the tumor suppressor p53, germline genetic deletion of AMPK β1 accelerates the appearance of a T cell lymphoma that reduces lifespan compared to p53 deficiency alone...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28544224/quantification-of-specific-t-and-b-cells-immunological-markers-in-children-with-chronic-and-transient-itp
#11
Sarina Levy-Mendelovich, Atar Lev, Shraga Aviner, Nurit Rosenberg, Caim Kaplinsky, Nechama Sharon, Hagit Miskin, Aviya Dvir, Gili Kenet, Irit Eisen Schushan, Raz Somech
BACKGROUND: Immune thrombocytopenic purpura (ITP) is characterized by a transient (nonchronic) or permanent (chronic) decline in the number of platelets. Predicting the course of ITP, at the time of diagnosis, is of importance. Here we studied at diagnosis, clinical and immunological parameters in order to distinguish between different courses. The latter included the measure of new B and T cells using quantification of kappa-deleting recombination excision circles (KRECs) and T-cell receptor excision circles (TRECs), respectively...
May 22, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28544101/belatacept-combined-with-transient-calcineurin-inhibitor-therapy-prevents-rejection-and-promotes-improved-long-term-renal-allograft-function
#12
A B Adams, J Goldstein, C Garrett, R Zhang, R E Patzer, K A Newell, N A Turgeon, A S Chami, A Guasch, A D Kirk, S O Pastan, T C Pearson, C P Larsen
Belatacept, a T cell costimulation-blocker demonstrated superior renal function, lower cardiovascular risk, and improved graft/patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011 we have utilized belatacept-based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n=535) to a historical cohort receiving a tacrolimus-based protocol (n=205)...
May 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28543977/abnormal-ratio-of-cd57-cells-to-cd56-cells-in-women-with-recurrent-implantation-failure
#13
Ruiwei Jiang, Guijun Yan, Jun Xing, Zhilong Wang, Yong Liu, Hongyan Wu, Xiangshan Fan, Jianjun Zhou, Lijun Ding, Haixiang Sun
PROBLEM: To define a more precise parameter for a better understanding of natural killer (NK) cells and its relation with regulatory T cells (Tregs) in women with recurrent implantation failure (RIF). METHOD OF STUDY: The percentages of CD56+ cells, CD57+ cells and Foxp3+ cells in the endometrium and blood from 23 normal controls and 32 women with RIF were measured by immunocytochemistry and flow cytometry. RESULTS: Women with RIF had significantly increased ratio of CD57+ cells to CD56+ cells in both the endometrium (P<...
May 20, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28543699/immune-and-molecular-correlates-in-melanoma-treated-with-immune-checkpoint-blockade
#14
REVIEW
Elizabeth H Byrne, David E Fisher
Immunotherapy for metastatic melanoma has a decades-long history, and the relatively recent use of checkpoint inhibitors has revolutionized treatment. Durable and sometimes complete remission of metastatic melanoma is now achievable in some patients who receive checkpoint-blocking therapy. However, it is unclear why some patients fare better than others. This review highlights several molecular indicators of response to checkpoint inhibition in metastatic melanoma, focusing on tumor programmed death ligand 1 expression, major histocompatibility complex class I expression, mutational load in the tumor, and T-cell infiltration into the tumor...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543698/adoptive-t-cell-therapy-an-overview-of-obstacles-and-opportunities
#15
REVIEW
Erez Nissim Baruch, Amy Lauren Berg, Michal Judith Besser, Jacob Schachter, Gal Markel
The therapeutic potential of adoptive cell therapy (ACT) in cancer patients was first acknowledged 3 decades ago, but it was an esoteric approach at the time. In recent years, technological advancements have transformed ACT into a viable therapeutic option that can be curative in some patients. In fact, current ACT response rates are 80% to 90% for hematological malignancies and 30% for metastatic melanoma refractory to multiple lines of therapy. Although these results are encouraging, there is still much to be done to fulfill ACT's potential, specifically with regard to improving clinical efficacy, expanding clinical indications, reducing toxicity, and increasing production and cost-effectiveness...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543637/evidence-of-the-immunomodulatory-role-of-dual-pi3k-mtor-inhibitors-in-graft-survival
#16
Valery Vilchez, Lilia Turcios, D Allan Butterfield, Mihail I Mitov, Cristin L Coquillard, Anthony J Brandon, Virgilius Cornea, Roberto Gedaly, Francesc Marti
The PI3K/mTOR signaling cascade is fundamental in T-cell activation and fate decisions. We showed the distinct regulation of PI3K/mTOR in regulatory and effector T-cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T-cell activities. Substantial adverse effects in long-term clinical usage of Rapamycin suggest the use of alternative treatments in restraining effector T-cell function in transplant patients. We hypothesize that dual PI3K/mTOR inhibitors may represent an immunosuppressant alternative...
May 24, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28543514/angioimmunoblastic-t-cell-lymphoma-more-than-a-disease-of-t-follicular-helper-cells
#17
François Lemonnier, Tak W Mak
Angioimmunoblastic T cell lymphoma (AITL) is one of the most frequent entities of peripheral T cell lymphoma. An AITL has two components: the AITL tumor cells that have a T follicular helper (TFH) cell phenotype, and a surrounding and extensive tumor microenvironment that is populated with various reactive cell types, including B cells. Recurrent TET2 mutations have been described in 50-80% of AITLs, possibly occurring in a hematopoietic progenitor cell. An article published recently in The Journal of Pathology describes the use of microdissection to isolate PD1(+) AITL tumor cells and CD20(+) B cells from the AITL microenvironment and to show that TET2 mutations are actually more frequent in these diseases than previously thought...
May 24, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28543380/chimeric-antigen-receptor-modified-t-cells-that-target-chemokine-receptor-ccr4-as-a-therapeutic-modality-for-t-cell-malignancies
#18
Liyanage P Perera, Meili Zhang, Masao Nakagawa, Michael N Petrus, Michiyuki Maeda, Marshall E Kadin, Thomas A Waldmann, Pin-Yu Perera
No abstract text is available yet for this article.
May 20, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28543181/loss-of-l-selectin-guided-cd8-but-not-cd4-cells-protects-against-ischemia-reperfusion-injury-in-a-steatotic-liver
#19
Vasantha L Kolachala, Sirish Palle, Ming Shen, Alayna Feng, Dmitry Shayakhmetov, Nitika A Gupta
BACKGROUND & AIMS: Steatotic liver responds with increased hepatocellular injury when exposed to an ischemic-reperfusion insult. Increasing evidence supports the role of immune cells as key mediators of this injury in a normal (lean) state, but data about their role in a steatotic liver are practically non-existent. The objective of the current study was to delineate contribution of specific phenotypes of T cells and adhesion molecules in exacerbated cell death in steatotic liver injury...
May 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28543170/specific-activation-of-cd4-cd8-double-negative-t-cells-by-t-cruzi-derived-glycolipids-induces-a-pro-inflammatory-profile-associated-with-cardiomyopathy-in-chagas-patients
#20
Lívia Silva Araújo Passos, Luísa Mourão Dias Magalhães, Rodrigo Pedro Soares, Alexandre F Marques, Maria do Carmo Pereira Nunes, Kenneth J Gollob, Walderez Ornelas Dutra
Cardiomyopathy is the most severe outcome of Chagas disease, causing over 12,000 deaths/year. Immune cells participate in cardiomyopathy development either by direct tissue destruction, or by driving inflammation. We have shown that CD4-CD8- (double negative - DN) T cells are major sources of inflammatory and anti-inflammatory cytokines, associated with the cardiac (CARD) and indeterminate (IND) forms of Chagas disease, respectively. Here, we sought to identify Trypanosoma cruzi derived components that lead to activation of DN T cells in Chagas patients...
May 24, 2017: Clinical and Experimental Immunology
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