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https://www.readbyqxmd.com/read/28096390/modification-of-host-dendritic-cells-by-microchimerism-derived-extracellular-vesicles-generates-split-tolerance
#1
William Bracamonte-Baran, Jonathan Florentin, Ying Zhou, Ewa Jankowska-Gan, W John Haynes, Weixiong Zhong, Todd V Brennan, Partha Dutta, Frans H J Claas, Jon J van Rood, William J Burlingham
Maternal microchimerism (MMc) has been associated with development of allospecific transplant tolerance, antitumor immunity, and cross-generational reproductive fitness, but its mode of action is unknown. We found in a murine model that MMc caused exposure to the noninherited maternal antigens in all offspring, but in some, MMc magnitude was enough to cause membrane alloantigen acquisition (mAAQ; "cross-dressing") of host dendritic cells (DCs). Extracellular vesicle (EV)-enriched serum fractions from mAAQ(+), but not from non-mAAQ, mice reproduced the DC cross-dressing phenomenon in vitro...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28086852/pd-l1-expression-in-papillary-renal-cell-carcinoma
#2
Takanobu Motoshima, Yoshihiro Komohara, Chaoya Ma, Arni Kusuma Dewi, Hirotsugu Noguchi, Sohsuke Yamada, Toshiyuki Nakayama, Shohei Kitada, Yoshiaki Kawano, Wataru Takahashi, Masaaki Sugimoto, Motohiro Takeya, Naohiro Fujimoto, Yoshinao Oda, Masatoshi Eto
BACKGROUND: The immune escape or tolerance of cancer cells is considered to be closely involved in cancer progression. Programmed death-1 (PD-1) is an inhibitory receptor expressed on activating T cells, and several types of cancer cells were found to express PD-1 ligand 1 (PD-L1) and ligand 2 (PD-L2). METHODS: In the present study, we investigated PD-L1/2 expression in papillary renal cell carcinoma (pRCC). RESULT: We found PD-L1 expression in 29 of 102 cases, but no PD-L2 expression was seen...
January 13, 2017: BMC Urology
https://www.readbyqxmd.com/read/28076863/adverse-renal-effects-of-immune-checkpoint-inhibitors-a-narrative-review
#3
Rimda Wanchoo, Sabine Karam, Nupur N Uppal, Valerie S Barta, Gilbert Deray, Craig Devoe, Vincent Launay-Vacher, Kenar D Jhaveri
BACKGROUND: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. SUMMARY: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity...
January 12, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28076847/programmed-cell-death-ligand-1-expression-predicts-survival-in-patients-with-gastric-carcinoma-with-microsatellite-instability
#4
Junhun Cho, Jeeyun Lee, Heejin Bang, Seung Tae Kim, Se Hoon Park, Ji Yeong An, Min Gew Choi, Joon Ho Lee, Tae Sung Sohn, Jae Moon Bae, Won Ki Kang, Sung Kim, Kyoung-Mee Kim
Programmed death-ligand 1 (PD-L1) is expressed in a subgroup of gastric cancers that may benefit from immunotherapy. Microsatellite instability-high (MSI-H) is a potential predictive factor for response to immunotherapy targeting the PD-1 or its ligand PD-L1. The relationship between PD-L1 expression and MSI-H status remains poorly understood. In this study, we investigated PD-L1 expression in patients with MSI-H gastric cancer. We analyzed PD-L1 expression in 78 MSI-H gastric cancer tissue samples using immunohistochemistry...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075442/increased-expression-of-pd%C3%A2-l1-by-the-human-papillomavirus-16-e7-oncoprotein-inhibits-anticancer-immunity
#5
Chaoqi Liu, Jiao Lu, Huiqun Tian, Wei Du, Lin Zhao, Jing Feng, Ding Yuan, Zhiying Li
Cytotoxic T lymphocyte dysfunction is frequently associated with PD‑L1/PD‑1 pathway activation, and is a principal obstacle in cancer therapy. In the present study, the mechanisms underlying the human papillomavirus (HPV)‑induced evasion of cervical cancer cells to the host immune system via the programmed death ligand  1/programmed death 1 (PD‑L1/PD‑1) signaling pathway was investigated. A significant increase in the expression of the HPV16E7 viral protein and PD‑L1 in cervical tissues was observed when compared with normal cervical tissues...
January 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28074529/epigenetic-mediated-immune-suppression-of-positive-co-stimulatory-molecules-in-chemoresistant-ovarian-cancer-cells
#6
Ercan Cacan
The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Ovarian cancer creates a suppressive microenvironment to escape immune elimination; however, the molecular mechanisms are poorly understood, and it is unclear whether chemotherapeutic drugs exert an immunoreactive or immunosuppressive effect on the tumor microenvironment. 4-1BB ligand (4-1BBL/CD157) and OX-40 ligand (OX-40L/CD252) are important regulators of effector cytotoxic T-cells activity...
January 11, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28073774/temporally-distinct-pd-l1-expression-by-tumor-and-host-cells-contributes-to-immune-escape
#7
Takuro Noguchi, Jeffrey P Ward, Matthew M Gubin, Cora D Arthur, Sang Hun Lee, Jasreet Hundal, Mark Selby, Robert F Graziano, Elaine R Mardis, Alan J Korman, Robert D Schreiber
Antibody blockade of Programmed Death-1 (PD-1) or its ligand, PD-L1, has led to unprecedented therapeutic responses in certain tumor-bearing individuals, but PD-L1 expression's prognostic value in stratifying cancer patients for such treatment remains unclear. Reports conflict on the significance of correlations between PD-L1 on tumor cells and positive clinical outcomes to PD-1/PD-L1 blockade. We investigated this issue using genomically-related, clonal subsets from the same methylcholanthrene-induced sarcoma: a highly immunogenic subset that is spontaneously eliminated in vivo by adaptive immunity and a less immunogenic subset that forms tumors in immunocompetent mice, but is sensitive to PD-1/PD-L1 blockade therapy...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28072859/increased-pd-1-expression-and-altered-t-cell-repertoire-diversity-predict-mortality-in-patients-with-septic-shock-a-preliminary-study
#8
Atsutoshi Tomino, Masanobu Tsuda, Ruri Aoki, Yuka Kajita, Masamitsu Hashiba, Tsuguaki Terajima, Hideki Kano, Naoshi Takeyama
Sepsis causes impairment of innate and adaptive immunity by multiple mechanisms, including depletion of immune effector cells and T cell exhaustion. Although lymphocyte dysfunction is associated with increased mortality and potential reactivation of latent viral infection in patients with septic shock, the relation between viral reactivation and lymphocyte dysfunction is obscure. The objectives of this study were 1) to determine the relation of lymphocyte dysfunction to viral reactivation and mortality, and 2) to evaluate recovery of lymphocyte function during septic shock, including T cell receptor (TCR) diversity and the expression of programmed death 1 (PD-1)...
2017: PloS One
https://www.readbyqxmd.com/read/28072716/pneumonitis-in-cancer-patients-receiving-anti-pd-1-and-radiotherapies-three-case-reports
#9
Chieh-Sheng Lu, Jin-Hwang Liu
INTRODUCTION: In development of novel therapies for the treatment of patient with cancer, the use of radiotherapy (RT) can produce significant local control and, in recent studies, has also been shown to mediate anti-tumor responses at distant sites by triggering and enhancing the endogenous cellular immune responses. Although RT induces an abscopal effect in some patients due to enhanced immune response to the tumor, immune-escape mechanisms, including up-regulation of programmed death-ligand 1 (PD-L1) on tumor cells, limit this benefit in other patients...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28067827/clinical-significance-and-prognostic-relevance-of-microsatellite-instability-in-sporadic-colorectal-cancer-patients
#10
REVIEW
Angelika Copija, Dariusz Waniczek, Andrzej Witkoś, Katarzyna Walkiewicz, Ewa Nowakowska-Zajdel
Microsatellite instability (MSI) is a marker of the replication error phenotype. It is caused by impaired DNA mismatch repair processes (MMR), resulting in ineffectiveness of the mechanisms responsible for the DNA replication precision and postreplicative DNA repair. MSI underlies the pathogenesis of 10%-20% of colorectal cancer (CRC) cases. The data about the potential value of MMR status as a predictive factor for 5-fluorouracil (FU)-based chemotherapy remain unclear. According to National Comprehensive Cancer Network updated guidelines, MSI testing is recommended for all patients with stage II CRC because patients with MSI-H (high-frequency MSI) tumour may have a good prognosis and obtain no benefit from 5-FU-based adjuvant chemotherapy...
January 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28066541/ultrastructural-changes-during-osteogenic-differentiation-in-mesenchymal-stromal-cells-cultured-in-alginate-hydrogel
#11
Jakub Grzesiak, Agnieszka Śmieszek, Krzysztof Marycz
BACKGROUND: Osteogenic differentiation of mesenchymal stem cells has been extensively investigated with regards to different aspects, including the analysis of cell intracellular and extracellular proteome, cell gene expression pattern, and morphology. During the osteogenic differentiation, osteoblasts produce and release specific proteins, like osteocalcin and osteopontin. Simultaneously, cells produce the extracellular matrix (ECM) that resembles the bone ECM, with high quantity of calcium and phosphorus...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28063623/immune-checkpoint-inhibitors-in-lung-cancer-an-unheralded-opportunity
#12
R Marshall, A Popple, T Kordbacheh, J Honeychurch, C Faivre-Finn, T Illidge
Lung cancer remains the leading cause of cancer-related death worldwide, with non-small cell lung cancer accounting for 85% of the disease. Over 70% of patients present with locally advanced, non-resectable or metastatic disease and despite improvements in chemoradiotherapy regimens and the development of molecularly targeted agents, 5 year survival rates remain poor, with acquired resistance to novel targeted therapies becoming a growing concern. Currently there remains an unmet need in effectively treating and inducing durable responses in advanced disease...
January 4, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28063173/identification-of-highly-connected-hub-genes-in-the-protective-response-program-of-human-macrophages-and-microglia-activated-by-alpha-b-crystallin
#13
Inge R Holtman, Malika Bsibsi, Wouter H Gerritsen, Hendrikus W G M Boddeke, Bart J L Eggen, Paul van der Valk, Markus Kipp, Johannes M van Noort, Sandra Amor
The glial stress protein alpha B-crystallin (HSPB5) is an endogenous agonist for Toll-like receptor 2 in CD14(+) cells. Following systemic administration, HSPB5 acts as a potent inhibitor of neuroinflammation in animal models and reduces lesion development in multiple sclerosis patients. Here, we show that systemically administered HSPB5 rapidly crosses the blood-brain barrier, implicating microglia as additional targets for HSPB5 along with peripheral monocytes and macrophages. To compare key players in the HSPB5-induced protective response of human macrophages and microglia, we applied weighted gene co-expression network analysis on transcript expression data obtained 1 and 4 h after activation...
January 7, 2017: Glia
https://www.readbyqxmd.com/read/28059852/immune-checkpoint-inhibitors-in-first-line-therapy-of-advanced-non-small-cell-lung-cancer
#14
Jordi Remon, Benjamin Besse
PURPOSE OF REVIEW: Evading immune destruction is a hallmark of cancer. The first therapeutic wave in immunotherapies comprised a series of monoclonal antibodies directed against the immune checkpoint molecules cytotoxic T-lymphocyte-associated protein 4, programmed death 1 (PD-1), and programmed death ligand-1 (PD-L1) revolutionizing the therapeutic landscape of advanced non-small cell lung cancer. They were validated initially as second-line treatment, becoming the new standard of care...
January 3, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28059094/heterogeneous-expression-of-pd-l1-in-pulmonary-squamous-cell-carcinoma-and-adenocarcinoma-implications-for-assessment-by-small-biopsy
#15
Thomas J Gniadek, Qing Kay Li, Ellen Tully, Samit Chatterjee, Sridhar Nimmagadda, Edward Gabrielson
Predicting response to checkpoint blockade therapy for lung cancer has largely focused on measuring programmed death-ligand 1 (PD-L1) expression on tumor cells. PD-L1 expression is geographically heterogeneous within many tumors, however, and we questioned whether small tissue samples, such as biopsies, might be sufficiently representative of PD-L1 expression for evaluating this marker in lung cancer tumors. To evaluate the extent of variability of PD-L1 expression in small tissue samples, and how that variability affects accuracy of overall assessment of PD-L1 in lung cancer, we scored immunohistochemical staining for PD-L1 in tissue microarray cores from a series of 79 squamous cell lung cancers and 71 pulmonary adenocarcinomas...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28059093/expression-of-pd-l1-and-presence-of-cd8-positive-t-cells-in-pre-treatment-specimens-of-locally-advanced-cervical-cancer
#16
Emeka K Enwere, Elizabeth N Kornaga, Michelle Dean, Theodora A Koulis, Tien Phan, Maria Kalantarian, Martin Köbel, Prafull Ghatage, Anthony M Magliocco, Susan P Lees-Miller, Corinne M Doll
Several of the cancer immunotherapies under investigation or in clinical use target the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling axis. PD-L1 expression in tumor samples has been used as a predictive marker for response to these therapeutics, and may also have independent prognostic utility when assessed along with immune cell markers. Our objectives were to assess the expression of PD-L1 in tumor specimens from a uniformly treated patient cohort with locally advanced cervical cancer, and to determine its prognostic significance along with the density of tumor-infiltrating T cells...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28058578/pd-l1-expression-and-tumor-infiltrating-pd-1-%C3%A2-lymphocytes-associated-with-outcome-in-her2-%C3%A2-breast-cancer-patients
#17
Julia Y S Tsang, Wai-Ling Au, Kwan-Yin Lo, Yun-Bi Ni, Thazin Hlaing, Jintao Hu, Siu-Ki Chan, Kui-Fat Chan, Sai-Yin Cheung, Gary M Tse
PURPOSE: Clinical trials showing programmed death (PD)-1-PD-ligand 1 (L1) axis as a promising therapeutic target in melanoma and non-small cell lung cancers have made the pathway a focus of recent attention. However, the data regarding PD-L1/PD-1 in breast cancer are inconsistent. Given the heterogeneity of breast cancers, the clinical relevance of PD-L1 and PD-1 tumor infiltrating lymphocytes (TIL) may vary according to subtypes of breast cancer. We aim to investigate PD-L1 expression in a large cohort of breast cancers and analyze its clinico-pathological as well as outcome relationship according to molecular subtypes...
January 5, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28057155/-level-of-soluble-programmed-death-1-ligand-1-in-peripheral-blood-of-patients-with-advanced-epidermal-growth-factor-receptor-mutated-lung-adenocarcinoma-and-its-clinical-implications
#18
L Q Zhang, Y Chen, X Pan, Y F Xing, M H Shi, Y J Chen
Objective: To analyze the expression of soluble programmed death ligand 1 (sPD-L1) in the serum of patients with advanced epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma and to explore its clinical implications. Methods: Seventy-two patients with EGFR mutated advanced lung adenocarcinoma (EGFR mutation group) were included from the Department of Respiratory Diseases in The Second Affiliated Hospital of Soochow University from May 2015 to July 2016. Thirty-one patients with advanced EGFR wild type (WT) lung adenocarcinoma [EGFR WT group, diagnosed via mini specimens from bronchoscopy or transthoracic needle aspiration biopsy (TNAB), matching in sex, age and tumor stage with EGFR mutation group] were also enrolled as controls...
December 27, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28056206/efficacy-and-safety-of-nivolumab-alone-or-in-combination-with-ipilimumab-in-patients-with-mucosal-melanoma-a-pooled-analysis
#19
Sandra P D'Angelo, James Larkin, Jeffrey A Sosman, Celeste Lebbé, Benjamin Brady, Bart Neyns, Henrik Schmidt, Jessica C Hassel, F Stephen Hodi, Paul Lorigan, Kerry J Savage, Wilson H Miller, Peter Mohr, Ivan Marquez-Rodas, Julie Charles, Martin Kaatz, Mario Sznol, Jeffrey S Weber, Alexander N Shoushtari, Mary Ruisi, Joel Jiang, Jedd D Wolchok
Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28056089/helicobacter-pylori-promote-b7-h1-expression-by-suppressing-mir-152-and-mir-200b-in-gastric-cancer-cells
#20
Gengchen Xie, Wei Li, Ruidong Li, Ke Wu, Ende Zhao, Yu Zhang, Peng Zhang, Liang Shi, Di Wang, Yuping Yin, Rui Deng, Kaixiong Tao
The most common cause of gastric cancer is infection with helicobacter pylori (HP), but the associated molecular mechanism is not well understood. In the present study, we found a marked increase in the expression of B7-H1, a member of the B7 co-stimulatory family of molecules that bind to programmed death-1 (PD-1) and play a critical immunoregulatory role in the cell-mediated immune response, in HP-positive gastric cancer tissue. Infection of cultured gastric cancer cells with HP promoted B7-H1 expression and inhibited miR-152 and miR-200b expression...
2017: PloS One
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