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https://www.readbyqxmd.com/read/29655565/the-tolerogenic-role-of-ifn-%C3%AE
#1
REVIEW
Primož Rožman, Urban Švajger
Due to its extremely pleiotropic nature, the complex effects of IFN-γ exerted both on immune and non-immune cell types still remain only partially understood. The longstanding view of IFN-γ as being a predominantly inflammatory cytokine is constantly challenged by increasing demonstrations of its direct or indirect regulatory roles. Interferon-γ can exert tolerogenic effects on both innate and adaptive immune cell types, promoting tolerance of various antigen-presenting cells, and augmenting function and differentiation of regulatory T cells, respectively...
April 7, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29643764/the-idh1-mutation-induced-oncometabolite-2-hydroxyglutarate-may-affect-dna-methylation-and-expression-of-pd-l1-in-gliomas
#2
Luyan Mu, Yu Long, Changlin Yang, Linchun Jin, Haipeng Tao, Haitao Ge, Yifan E Chang, Aida Karachi, Paul S Kubilis, Gabriel De Leon, Jiping Qi, Elias J Sayour, Duane A Mitchell, Zhiguo Lin, Jianping Huang
Background: Malignant gliomas are heterogeneous brain tumors with the potential for aggressive disease progression, as influenced by suppressive immunoediting. Given the success and enhanced potential of immune-checkpoint inhibitors in immunotherapy, we focused on the connections between genetic alterations affected by IDH1 mutations and immunological landscape changes and PDL-1 expression in gliomas. Methods: Paired surgically resected tumors from lower-grade gliomas (LGGs) and glioblastomas (GBM) were investigated, and a genetic analysis of patients' primary tumor samples culled from TCGA datasets was performed...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29610255/pdl-1-blockade-prevents-t-cell-exhaustion-inhibits-autophagy-and-promotes-clearance-of-leishmania-donovani
#3
Samar Habib, Abdeljabar El Andaloussi, Khaled Elmasry, Aya Handoussa, Manar Azab, Aliaa Elsawey, Ayman Al-Hendy, Nahed Ismail
Leishmania donovani ( L. donovani ) is a causative pathogen of potentially-fatal visceral leishmaniasis (VL). Therapeutic agents are available; however, their use is limited due to high cost, serious side effects, and development of antimicrobial resistance. Protective immunity against VL depends on CD4+ Th1 cell-mediated immunity. Studies have shown that progression of VL is due to exhaustion of T cells; however, the mechanism involved is not clearly understood. Here, we examined the role of PD1/PDL-1 in the pathogenesis of VL using murine model of VL...
April 2, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29594918/squamous-cell-papillomatosis-in-the-setting-of-recurrent-respiratory-papillomatosis
#4
Pasha L Bentley, Michael J Coulter, Brenda L Nelson
A 23 year old male presented to the Otolaryngology clinic with 6 months of hoarseness and poor voice projection without improvement from speech therapy or medical anti-reflux medication. Upon examination he was found to have multiple polypoid lesions emanating from bilateral false vocal folds, left true vocal fold, and the anterior commissure. Biopsy and potassium titanyl phosphate (KTP) laser ablation with bevacizumab injection provided treatment and confirmed the clinical suspicion of squamous cell papilloma...
March 28, 2018: Head and Neck Pathology
https://www.readbyqxmd.com/read/29573129/effect-of-periodontal-ligament-removal-with-gauze-prior-to-delayed-replantation-in-rabbit-incisors-on-rate-of-replacement-resorption
#5
Manal Maslamani, Bobby Joseph, Severino Gabato, Lars Andersson
An avulsed tooth should ideally be replanted as soon as possible. Periodontal ligament (PDL) cells may survive for a short time in dry storage or storage in some physiologic media, enabling healing with normal PDL.1,2 However, after delayed replantation, when the extra oral drying time is longer than 60 min, the cells of the PDL will not survive.2-8 Despite this, even after long periods of dry extra oral time, delayed replantation is recommended although these PDL cells are necrotic.9,10 In such teeth ankylosis and osseous replacement are unavoidable, and the tooth will be eventually lost...
March 23, 2018: Dental Traumatology: Official Publication of International Association for Dental Traumatology
https://www.readbyqxmd.com/read/29569115/-systemic-immune-checkpoint-inhibition-a-promising-treatment-for-urological-tumors
#6
REVIEW
F C Roos, C Becker, M B Stope, I Tsaur
Improved understanding of the immunomodulatory interactions between tumor cells and immune cells has led to new and promising systemic therapeutic approaches in the first- and second-line therapy of urological tumors. Particularly in the case of urothelial carcinoma, for the first time in 20 years, checkpoint inhibitors (PD-1 and PDL-1 inhibitors) provide well-tolerated therapy that achieves response rates of >20% that can be sustained over the long term. This review explains the approach of immunotherapy and summarizes the current phase III clinical situation on urothelial carcinoma and renal cell carcinoma...
March 22, 2018: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/29545367/a-dominant-role-for-regulatory-t-cells-in-protecting-females-against-pulmonary-hypertension
#7
Rasa Tamosiuniene, Olga Manouvakhova, Paul Mesange, Toshie Saito, Jin Qian, Mrinmoy Sanyal, Yu-Chun Lin, Linh P Nguyen, Amir Luria, Allen B Tu, Joshua M Sante, Marlene Rabinovitch, Desmond J Fitzgerald, Brian B Graham, Aida Habtezion, Norbert F Voelkel, Laure Aurelian, Mark R Nicolls
<u>Rationale:</u> Pulmonary arterial hypertension (PH) is a life-threatening condition associated with immune dysregulation and abnormal regulatory T cell (Treg) activity, but it is currently unknown whether and how abnormal Treg function differentially affects males and females. <u>Objective:</u> To evaluate whether and how Treg-deficiency differentially affects male and female rats in experimental PH. <u>Methods and Results:</u> Male and female athymic rnu/rnu rats, lacking Tregs, were treated with the vascular endothelial growth factor receptor-2 (VEGFR2) inhibitor SU5416 or chronic hypoxia and evaluated for PH; some animals underwent Treg immune reconstitution (IR) before SU5416 administration...
March 15, 2018: Circulation Research
https://www.readbyqxmd.com/read/29541402/semaphorin-4d-in-human-head-and-neck-cancer-tissue-and-peripheral-blood-a-dense-fibrotic-peri-tumoral-stromal-phenotype
#8
Roshanak Derakhshandeh, Sonia Sanadhya, Kyu Lee Han, Haiyan Chen, Olga Goloubeva, Tonya J Webb, Rania H Younis
The search for stromal biomarkers in carcinoma patients is a challenge in the field. Semaphorin 4D (Sema4D), known for its various developmental, physiological and pathological effects, plays a role in pro and anti-inflammatory responses. It is expressed in many epithelial tumors including head and neck squamous cell carcinoma (HNSCC). Recently, we found that HNSCC-associated Sema4D modulates an immune-suppressive, tumor-permissible environment by inducing the expansion of myeloid derived suppressor cells. The purpose of this study was to determine the value of Sema4D as a biomarker for the peri-tumoral stromal phenotype in human HNSCC...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29518754/endocrine-sequelae-of-immune-checkpoint-inhibitors
#9
REVIEW
Georgia Ntali, Eva Kassi, Maria Alevizaki
Cancer immunotherapy has introduced a novel class of drugs known as immune checkpoint inhibitors (ICIs). They enhance antitumour immunity by blocking negative regulators (checkpoints) of T cell function that exist on both immune and tumour cells. ICIs targeting CTLA-4 and PD-1/PDL-1 have dramatically changed the outcome of patients with several advanced-stage malignancies but they may lead to a variety of inflammatory toxicities and autoimmune consequences. The main endocrine immune-related adverse events (IRAEs) include hypophysitis, primary thyroid dysfunction, adrenalitis and type 1 diabetes mellitus...
October 2017: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29489031/blood-tolerogenic-monocytes-and-low-proportions-of-dendritic-cell-subpopulations-are-hallmarks-of-human-tuberculosis
#10
Violette Dirix, Véronique Corbière, Chloé Wyndham-Thomas, Elodie Selis, Sabine Allard, Maya Hites, Laetitia Aerts, Thomas Giese, Françoise Mascart
BACKGROUND: The immune mechanisms underlying the pathogenesis of tuberculosis (TB) need better understanding to improve TB management, as the disease still causes more than 1.5 million deaths annually. This study tested the hypothesis that a modulation of the proportions or activation status of APC during Mycobacterium tuberculosis infection may impact on the course of the disease. PROCEDURE: Proportions of circulating APC subsets and the expression of stimulatory (CD86), inhibitory (ILT-3, ILT-4, ILT-7), or apoptosis-inducing (PDL-1, PDL-2) molecules were analyzed in 2 independent cohorts, on blood monocytes and dendritic cell (DC) subsets from patients with active or latent TB infection (aTB /LTBI) and from uninfected subjects...
February 28, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29483408/-significance-of-immune-cell-infiltration-in-gastric
#11
Hiroaki Tanaka, Tatsuro Tamura, Yoshihiro Okita, Mami Yoshii, Mao Tokumoto, Yukie Go, Chie Sakimura, Soichiro Hiramatsu, Junya Nishimura, Yoshihito Yamagoe, Masakazu Yashiro, Yuichiro Miki, Takahiro Toyokawa, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira
There are many reports on the association between infiltrating immune cells andcancer prognosis. It is generally thought that cancer cells escape from the immune surveillance system in vivo. Cells associatedwith tumor immunosuppressive mechanisms include macrophages, regulatory T cells, bone marrow-derived immunosuppressive cells(MDSC), andneutrophils. These immunosuppressive cells enhance the production of TGF-b andIL -10 andthe expression of PDL-1 by cytokines producedby stromal cells such as cancer cells andfibroblasts, thereby inducing cytotoxic T cells lymphocytes(CTL)...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29475913/expression-and-clinical-significance-of-claudin-7-pdl-1-pten-c-kit-c-met-c-myc-alk-ck5-6-ck17-p53-egfr-ki67-p63-in-triple-negative-breast-cancer-a-single-centre-prospective-observational-study
#12
Chloe Constantinou, Savvas Papadopoulos, Eirini Karyda, Athanasios Alexopoulos, Niki Agnanti, Anna Batistatou, Haris Harisis
BACKGROUND/AIM: To explore the relationship between p53, p63, c-kit, Ki67, cMet, claudin7, CK5/6, CK17, AR, PTEN, EGFR, ALK, PDL-1 and c-MYC expression with the clinicopathological features of triple- negative breast cancer. MATERIALS AND METHODS: Immunohistochemistry was performed in 84 triple-negative breast cancer samples. RESULTS: A statistically significant relationship between tumour grade and claudin-7 (p=0.004) and between protein p53 and positive lymph nodes (p=0...
March 2018: In Vivo
https://www.readbyqxmd.com/read/29463302/the-impact-of-pd-l1-on-survival-and-value-of-the-immune-check-point-inhibitors-in-non-small-cell-lung-cancer-proposal-policies-and-perspective
#13
Helmy M Guirgis
BACKGROUND: The impact of programmed death receptor-ligand1 (PD-L1) on costs and value of the immune check point inhibitors (ICPI) has received minimal attention. OBJECTIVES: 1- Design a sliding scale to grade survival in 2nd-line non-small-cell lung cancer (NSCLC). 2- Compare costs and value of Nivolumab (Nivo), Atezolizumab (Atezo) and Pembrolizumab (Pembro) vs. Docetaxel (Doc). METHODS: Previously reported median overall survival (OS) and prices posted by parent company were utilized...
February 20, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29439008/pd-1-and-pd-l1-expression-in-thymic-epithelial-tumours-and-non-neoplastic-thymus
#14
Emine Kilic Bagir, Arbil Acikalin, Alper Avci, Derya Gumurdulu, Semra Paydas
AIMS: We explored the relationships between programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression and the pathological and clinical features of thymic epithelial tumours and thymic hyperplasia. METHODS: We evaluated PD-1 and PDL-1 expressions within epithelial and microenvironmental components in thymic epithelial tumours (n=44) and thymic hyperplasias (n=8), immunohistochemically. We compared the results with demographic, clinical and histopathological features of the cases...
February 8, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29368051/role-of-immunotherapy-in-bladder-cancer-past-present-and-future
#15
REVIEW
Sabeeh-Ur-Rehman Butt, Laeeq Malik
As research focus in oncology has recently shifted from oral targeted therapy to immunomodulation, the era of successful drug development in bladder cancer has just begun. This has led to unprecedented approval of five immunotherapeutic agents by regulatory agencies for metastatic bladder cancer within a span of 12 months. With an initial triumph of anti-programmed cell death-1 (anti-PD-1) and anti-programmed cell death ligand-1 (anti-PDL-1) drugs, ongoing efforts are aimed at identification and validation of new druggable immune targets to consolidate the initial gains...
January 24, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29362129/proportion-of-cd4-and-cd8-tumor-infiltrating-lymphocytes-predicts-survival-in-persistent-recurrent-laryngeal-squamous-cell-carcinoma
#16
Rebecca Hoesli, Andrew C Birkeland, Andrew J Rosko, Mohamad Issa, Kelsey L Chow, Nicole L Michmerhuizen, Jacqueline E Mann, Steven B Chinn, Andrew G Shuman, Mark E Prince, Gregory T Wolf, Carol R Bradford, Jonathan B McHugh, J Chad Brenner, Matthew E Spector
Tumor infiltrating lymphocytes (TILs) have been shown to be an important prognostic factor in patients with previously untreated head and neck cancer. After organ preservation therapy for laryngeal cancer and subsequent persistence/recurrence, the prognostic value of TILs is unknown. Our goal was to determine if TILs have value as a prognostic biomarker in patients with surgically salvageable persistent/recurrent laryngeal squamous cell carcinoma. Levels of TILs were quantified on tissue microarrays from 183 patients undergoing salvage total laryngectomy for persistent/recurrent laryngeal cancer after radiation or chemoradiation between 1997 and 2014...
February 2018: Oral Oncology
https://www.readbyqxmd.com/read/29344157/expression-and-clinical-significance-of-programmed-death-1-on-lymphocytes-and-programmed-death-ligand-1-on-monocytes-in-the-peripheral-blood-of-patients-with-cervical-cancer
#17
Ying Zhang, Weipei Zhu, Xueguang Zhang, Qiuxia Qu, Liyuan Zhang
The programmed death-1 (PD-1) signaling pathway serves a critical role in immune regulation and tolerance by suppressing the activation and proliferation of T cells. The aim of the present study was to investigate the effect of PD-1 and programmed death-ligand 1 (PD-L1) on the development of cervical carcinoma and cervical intraepithelial neoplasia (CIN). A total of 40 healthy controls (HC), 40 patients with CIN and 66 newly diagnosed cervical cancer patients were recruited. The expression level of PD-1 expression on peripheral cluster of differentiation (CD)4+ and CD8+ T cells and PD-L1 on monocytes was analyzed by flow cytometry...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29321652/innate-ifn-%C3%AE-ameliorates-experimental-autoimmune-encephalomyelitis-and-promotes-myeloid-expansion-and-pdl-1-expression
#18
Madeleine P J White, Gill Webster, Faith Leonard, Anne Camille La Flamme
The innate immune system plays a central role in the immune-mediated pathology of multiple sclerosis, and is a therapeutic target for progressive disease. Recently, it has been demonstrated that MIS416, a novel immunomodulatory microparticle that activates NOD-2 and TLR-9-signaling, has disease-modifying activity in multiple sclerosis models. This activity is dependent on innate IFN-γ; however, the precise immune regulatory mechanisms amplified by MIS416 have not previously been determined. Using the experimental autoimmune encephalomyelitis model, MIS416 treatment was associated with IFN-γ-dependant expansion of Treg number and increased suppressive function; however, these cells did not account for disease reduction...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29228684/atorvastatin-downregulates-co-inhibitory-receptor-expression-by-targeting-ras-activated-mtor-signalling
#19
Isobel Okoye, Afshin Namdar, Lai Xu, Nicole Crux, Shokrollah Elahi
Regulation of T cell function in the steady state is mediated by co-inhibitory receptors or immune checkpoints such as PD-1, CTLA-4, TIM-3 and LAG-3. Persistent antigen stimulation, during chronic viral infections and cancer, results in sustained expression of multiple co-inhibitory receptors and subsequently poor effector T cell function. Immune checkpoint blockade using monoclonal antibodies against PD-1, PDL-1 and CTLA-4 has been implemented as an immunotherapy strategy- resulting in restoration of T cell function and reduction of viral load or tumour growth...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29182990/patterns-of-responses-in-metastatic-nsclc-during-pd-1-or-pdl-1-inhibitor-therapy-comparison-of-recist-1-1-irrecist-and-irecist-criteria
#20
M Tazdait, L Mezquita, J Lahmar, R Ferrara, F Bidault, S Ammari, C Balleyguier, D Planchard, A Gazzah, J C Soria, A Marabelle, B Besse, C Caramella
BACKGROUND: Immune checkpoint inhibitors are an important tool in the therapeutic strategy against metastatic non-small cell lung cancer (NSCLC); however, radiological evaluation is challenging due to the emergence of atypical patterns of responses. Several evaluation criteria have been proposed, such as the Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1, immune -related RECIST (irRECIST) and iRECIST, but have not been systematically compared in a homogeneous population...
January 2018: European Journal of Cancer
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