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https://www.readbyqxmd.com/read/28717940/alopecia-areata-a-comprehensive-review-of-pathogenesis-and-management
#1
REVIEW
Ralph M Trüeb, Maria Fernanda Reis Gavazzoni Dias
Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis...
July 17, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28716895/ctla4-promotes%C3%A2-tyk2-stat3-dependent-b-cell-oncogenecity
#2
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/28715352/commensal-bacterial-modulation-of-the-host-immune-response-to-ameliorate-pain-in-a-murine-model-of-chronic-prostatitis
#3
Stephen F Murphy, Anthony J Schaeffer, Joseph D Done, Marsha L Quick, Utkucan Acar, Praveen Thumbikat
The human commensal microflora plays an essential role in modulating the immune response to control homeostasis. Staphylococcus epidermidis, a commensal bacterium most commonly associated with the skin exerts such effects locally, modulating local immune responses during inflammation and preventing superinfection by pathogens such as Staphylococcus aureus. Although the prostate is considered by many to be sterile, multiple investigations have shown that small numbers of gram-positive bacterial species such as S...
August 2017: Pain
https://www.readbyqxmd.com/read/28697066/viral-induced-modulation-of-multiple-checkpoint-proteins-in-cancers
#4
Gerard J Nuovo, Virginia A Folcik, Cynthia Magro
Therapy with checkpoint inhibitors represents a major advance in cancer treatment. The purpose of this study was to examine the expression patterns of the checkpoint proteins programmed death ligand 1 (PD L1), PD L2, indoleamine 2,3-dioxygenase 1 (IDO1), and cytotoxic T-lymphocyte antigen 4 (CTLA4) in cancers including those associated with viral infections. Normal, noninflamed tissues rarely express checkpoint proteins with exceptions including the placenta and stomach. Expression of PD L1 was noted in 30%, PD L2 in 18%, IDO1 in 13%, and CTLA4 in 14% of 333 nonviral malignancies including endometrial, ovarian, lung, and breast cancers...
July 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28690850/agammaglobulinaemia-despite-terminal-b-cell-differentiation-in-a-patient-with-a-novel-lrba-mutation
#5
Nashat Al Sukaiti, Khwater AbdelRahman, Jalila AlShekaili, Sumaya Al Oraimi, Aisha Al Sinani, Nasser Al Rahbi, Vicky Cho, Matt Field, Matthew C Cook
Mutations in lipopolysaccharide-responsive vesicle trafficking, beach and anchor-containing protein (LRBA) cause immune deficiency and inflammation. Here, we are reporting a novel homozygous mutation in LRBA allele in 7-year-old Omani boy, born to consanguineous parents. He presented with type 1 diabetes, autoimmune haematological cytopenia, recurrent chest infections and lymphocytic interstitial lung disease. The patient was treated with CTLA4-Ig (abatacept) with good outcome every 2 weeks for a period of 3 months...
May 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28689001/immuno-oncologic-approaches-car-t-cells-and-checkpoint-inhibitors
#6
REVIEW
Francesca Gay, Mattia D'Agostino, Luisa Giaccone, Mariella Genuardi, Moreno Festuccia, Mario Boccadoro, Benedetto Bruno
Advances in understanding myeloma biology have shown that disease progression is not only the consequence of intrinsic tumor changes but also of interactions between the tumor and the microenvironment in which the cancer grows. The immune system is an important component of the tumor microenvironment in myeloma, and acting on the immune system is an appealing new treatment strategy. There are 2 ways to act toward immune cells and boost antitumor immunity: (1) to increase antitumor activity (acting on T and NK cytotoxic cells), and (2) to reduce immunosuppression (acting on myeloid-derived stem cells and T regulatory cells)...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28687929/periostin-promotes-ectopic-osteogenesis-of-ctla4-modified-bone-marrow-mesenchymal-stem-cells
#7
Fei Zhang, Zhigang Rong, Zhengdong Wang, Zehua Zhang, Dong Sun, Shiwu Dong, Jianzhong Xu, Fei Dai
The improved ectopic osteogenesis of cytotoxic T-lymphocyte-associated antigen 4-Ig-modified bone marrow mesenchymal stem cells (MSCs-CTLA4) has been demonstrated but the mechanisms involved remain to be determined. The extracellular matrix (ECM) has recently been reported to play a vital role in bone formation and periostin (POSTN) has been suggested as a key member in constructing the ECM in bone tissue. We found that POSTN expression in the MSCs-CTLA4 group is significantly enhanced compared with that in the MSCs group, not only in tissue-engineered bone (TEB) with femur heterotopic transplantation in vivo but also under the immune activation condition in vitro...
July 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28687658/the-effect-of-inhibitory-signals-on-the-priming-of-drug-hapten-specific-t-cells-that-express-distinct-v%C3%AE-receptors
#8
Andrew Gibson, Lee Faulkner, Maike Lichtenfels, Monday Ogese, Zaid Al-Attar, Ana Alfirevic, Philipp R Esser, Stefan F Martin, Munir Pirmohamed, B Kevin Park, Dean J Naisbitt
Drug hypersensitivity involves the activation of T cells in an HLA allele-restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell-priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses...
July 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28685773/inhibition-of-the-b7-h3-immune-checkpoint-limits-tumor-growth-by-enhancing-cytotoxic-lymphocyte-function
#9
Young-Hee Lee, Natalia Martin-Orozco, Peilin Zheng, Jing Li, Peng Zhang, Haidong Tan, Hyun Jung Park, Mira Jeong, Seon Hee Chang, Byung-Seok Kim, Wei Xiong, Wenjuan Zang, Li Guo, Yang Liu, Zhong-Jun Dong, Willem W Overwijk, Patrick Hwu, Qing Yi, Larry Kwak, Zhiying Yang, Tak W Mak, Wei Li, Laszlo G Radvanyi, Ling Ni, Dongfang Liu, Chen Dong
The interaction between tumor and the immune system is still poorly understood. Significant clinical responses have been achieved in cancer patients treated with antibodies against the CTLA4 and PD-1/PD-L1 checkpoints; however, only a small portion of patients responded to the therapies, indicating a need to explore additional co-inhibitory molecules for cancer treatment. B7-H3, a member of the B7 superfamily, was previously shown by us to inhibit T-cell activation and autoimmunity. In this study, we have analyzed the function of B7-H3 in tumor immunity...
July 7, 2017: Cell Research
https://www.readbyqxmd.com/read/28684632/immunodeficiency-in-pancreatic-adenocarcinoma-with-diabetes-revealed-by-comparative-genomics
#10
Yuanqing Yan, Ruli Gao, Thao L P Trinh, Maria Bartolomeo Grant
Purpose: Pancreatic adenocarcinomas (PAAD) often are not diagnosed until their late stages leaving no effective treatments. Currently immunotherapy provides a promising treatment option against this malignancy. However, a set of immunotherapy agents benefit patients with many types of cancer, but not PAAD. Sharing the origin in the same organ, diabetes and PAAD tend to occur concurrently. We aimed to identify the impact of diabetes on immunotherapy of PAAD by conducting a comparative genomics analysis.    <p>Experimental Design: We analyzed levels 3 PAAD genomics data (RNAseq, miRNAseq, DNA methylation, somatic copy number and somatic mutation) from TCGA and Firehose...
July 6, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28681901/dense-genotyping-of-immune-related-regions-identifies-loci-for-rheumatoid-arthritis-risk-and-damage-in-african-americans
#11
Maria I Danila, Vincent Albert Laufer, Richard J Reynolds, Qi Yan, Nianjun Liu, Peter K Gregersen, Annette Lee, Marlena Kern, Carl D Langefeld, Donna K Arnett, S Louis Bridges
Over 100 risk loci for rheumatoid arthritis (RA) have been identified in individuals of European and Asian descent, but the genetic basis for RA in African Americans is less well understood. We genotyped 610 African Americans with autoantibody positive RA and 933 African American controls on the ImmunoChip (iChip) array. Using multivariable regression we evaluated the association between iChip markers and the risk of RA and radiographic severity. The single nucleotide polymorphism (SNP) rs1964995 (OR = 1.97, p = 1...
June 29, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28680745/vaccination-targeting-human-her3-alters-the-phenotype-of-infiltrating-t-cells-and-responses-to-immune-checkpoint-inhibition
#12
Takuya Osada, Michael A Morse, Amy Hobeika, Marcio A Diniz, William R Gwin, Zachary Hartman, Junping Wei, Hongtao Guo, Xiao-Yi Yang, Cong-Xiao Liu, Kensuke Kaneko, Gloria Broadwater, H Kim Lyerly
Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28660994/altered-expression-of-ctla-4-cd28-vdr-and-cd45-mrna-in-t-cells-of-patients-with-hashimoto-s-thyroiditis-a-pilot-study
#13
Stana Tokić, Mario Štefanić, Ivan Karner, Ljubica Glavaš-Obrovac
INTRODUCTION: CD28/T-cell receptor (TCR)/cytotoxic T-lymphocyte antigen 4 (CTLA4) complex controls T-cell tolerance and autoimmunity in Hashimoto's thyroiditis (HT). In addition, CD45 protein tyrosine phosphatase (PTPase) and vitamin D receptor (VDR) cooperatively interact with the TCR complex to affect autoimmune processes central to the pathogenesis of HT. Nevertheless, their role in HT aetiology has been less well established. In this study, we aimed to explore mRNA expression levels of CTLA4, CD28, CD45, and VDR in T-cells, across different outcomes of HT...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28653570/the-second-wave-of-immune-checkpoint-inhibitor-tsunami-advance-challenges-and-perspectives
#14
Hampig Raphael Kourie, Gil Awada, Ahmad Awada
After the first wave of the tsunami of immune checkpoint inhibitors, 2016 was marked by the second wave, revealed by numerous US FDA approvals, publications and abstracts in relation with these drugs in different cancers and settings. First, we reported all new indications of anti-CTLA4, anti-programmed cell death protein 1 and anti-PDL1 approved by the FDA, the positive clinical trials published and the abstracts reported at important scientific meetings during 2016. Then, we highlighted the updates on debatable issues related to checkpoint inhibitors, since the first wave published in a previous issue...
June 2017: Immunotherapy
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore-functions-of-tumor-infiltrating-t-cells-in-hepatocellular-carcinomas
#15
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), downregulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase anti-tumor immunity in patients with melanoma, non-small cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4(+) and CD8(+) T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
June 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#16
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28642883/genetic-polymorphisms-of-cytotoxic-t-lymphocyte-antigen-4-in-primary-biliary-cholangitis-a-meta-analysis
#17
REVIEW
Xing-Chen Yang, Masayuki Fujino, Song-Jie Cai, Shao-Wei Li, Chi Liu, Xiao-Kang Li
BACKGROUND AND AIM: The connection between gene polymorphisms of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and primary biliary cholangitis (PBC) is still vague and blurred. The purpose of this study is to precisely estimate the association of the polymorphisms of CTLA4 with the risk of PBC by using a meta-analysis. METHODS: PubMed and the Chinese National Knowledge Infrastructure (CNKI) database were used to search correlative literatures, and the documents which were about the relationships between the polymorphisms of CTLA4 (rs231775, rs231725, rs3087243, and rs5742909) and PBC were collected as of June 2016...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28639886/a-competing-endogenous-rna-network-identifies-novel-mrna-mirna-and-lncrna-markers-for-the-prognosis-of-diabetic-pancreatic-cancer
#18
Kanyu Yao, Qi Wang, Jianhua Jia, Haiping Zhao
Pancreatic cancer (PaC) is highly associated with diabetes mellitus (DM). However, the mechanisms are insufficient. The study aimed to uncover the underlying regulatory mechanism on diabetic PaC and find novel biomarkers for the disease prognosis. Two RNA-sequencing (RNA-seq) datasets, GSE74629 and GSE15932, as well as relevant data in TCGA were utilized. After pretreatment, differentially expressed genes (DEGs) or miRNAs (DEMs) or lncRNAs (DELs) between diabetic PaC and non-diabetic PaC patients were identified, and further examined for their correlations with clinical information...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28638849/refractory-t-cell-anergy-and-rapidly-fatal-progressive-multifocal-leukoencephalopathy-after-prolonged-ctla4-therapy
#19
Manon Dekeyser, Marie-Ghislaine de Goër de Herve, Houria Hendel-Chavez, Céline Labeyrie, David Adams, Ghaïdaa Adebs Nasser, Jacques Gasnault, Antoine Durrbach, Yassine Taoufik
Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease due to central nervous system replication of the human polyomavirus JC virus (JCV) in immunosuppressed patients. The only effective therapeutic approach is to restore anti-JCV T-cell responses. In this study, we describe a case of rapidly fatal PML with JCV T-cell anergy in a renal transplant patient treated with CTLA4-Ig (belatacept, a CD28-B7 costimulation blocker and T-cell anergy inducer). T-cell anergy could not be reversed despite several therapeutic approaches...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28638138/immune-regulation-by-oral-tolerance-induces-alternate-activation-of-macrophages-and-reduces-markers-of-plaque-destabilization-in-apob-tm2sgy-ldlr-tm1her-j-mice
#20
Lakshmi Narasimha Thota, Thiruvelselvan Ponnusamy, Sheena Philip, Xinjie Lu, Lakshmi Mundkur
Atherosclerosis is the leading cause for cardiovascular mortality. We determined the effect of multi-antigenic construct expressing three peptides AHC (ApoB100, HSP60 and outer membrane protein of chlamydia pneumonia) in stabilizing advanced atherosclerosis in Apob(tm2Sgy)/Ldlr(tm1Her/J) mice. Atherosclerosis was induced by feeding high fat diet (HFD) to mice for 10 weeks, followed by five oral dosing with purified AHC or ovalbumin on alternate days and continued on HFD for another 10 weeks. Tolerance was associated with significantly higher numbers of regulatory T cells both in aortic sinus and spleen with higher mRNA expression of CTLA4 (3 fold), Foxp3 (1...
June 21, 2017: Scientific Reports
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