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https://www.readbyqxmd.com/read/27936218/a-key-role-for-inhibins-in-dendritic-cell-maturation-and-function
#1
Roxana Olguín-Alor, Marisol de la Fuente-Granada, Laura C Bonifaz, Laura Antonio-Herrera, Eduardo A García-Zepeda, Gloria Soldevila
Inhibins are members of the TGFβ superfamily, which regulate many cellular processes including differentiation, proliferation, survival and apoptosis. Although initially described as hormones regulating the hypothalamus-pituitary-gonadal axis, based on their ability to antagonize Activins, our group has recently reported that they play a role in thymocyte differentiation and survival, as well as in thymic stromal cell maturation and nTreg generation. Here, we used Inhibin knock out mice (Inhα-/-) to investigate the role of Inhibins in peripheral dendritic cell maturation and function...
2016: PloS One
https://www.readbyqxmd.com/read/27934877/overexpression-and-gene-amplification-of-pd-l1-in-cancer-cells-and-pd-l1-immune-cells-in-epstein-barr-virus-associated-gastric-cancer-the-prognostic-implications
#2
Ruri Saito, Hiroyuki Abe, Akiko Kunita, Hiroharu Yamashita, Yasuyuki Seto, Masashi Fukayama
Cancer cells use PD-L1 to evade antitumor immunity through interaction with programmed cell death protein 1 (PD-1) on T cells. Recent whole-genome sequence studies revealed frequent gene amplification of PD-L1 in Epstein-Barr virus-associated gastric cancer (EBVaGC). To investigate the significance of PD-L1 in cancer cells and their microenvironment in EBVaGC, we studied PD-L1 expression by analysis of the public database and immunohistochemistry with fluorescent in situ hybridization (FISH) of the PD-L1 gene...
December 9, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27932443/pd-l1-blockade-enhances-response-of-pancreatic-ductal-adenocarcinoma-to-radiotherapy
#3
Abul Azad, Su Yin Lim, Zenobia D'Costa, Keaton Jones, Angela Diana, Owen J Sansom, Philipp Kruger, Stanley Liu, W Gillies McKenna, Omer Dushek, Ruth J Muschel, Emmanouil Fokas
Pancreatic ductal adenocarcinoma (PDAC) is considered a non-immunogenic tumor, and immune checkpoint inhibitor monotherapy lacks efficacy in this disease. Radiotherapy (RT) can stimulate the immune system. Here, we show that treatment of KPC and Pan02 murine PDAC cells with RT and gemcitabine upregulated PD-L1 expression in a JAK/Stat1-dependent manner. In vitro, PD-L1 inhibition did not alter radio- and chemosensitivity. In vivo, addition of anti-PD-L1 to high (12, 5 × 3, 20 Gy) but not low (6, 5 × 2 Gy) RT doses significantly improved tumor response in KPC and Pan02 allografts...
December 8, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27932067/nivolumab-plus-ipilimumab-as-first-line-treatment-for-advanced-non-small-cell-lung-cancer-checkmate-012-results-of-an-open-label-phase-1-multicohort-study
#4
Matthew D Hellmann, Naiyer A Rizvi, Jonathan W Goldman, Scott N Gettinger, Hossein Borghaei, Julie R Brahmer, Neal E Ready, David E Gerber, Laura Q Chow, Rosalyn A Juergens, Frances A Shepherd, Scott A Laurie, William J Geese, Shruti Agrawal, Tina C Young, Xuemei Li, Scott J Antonia
BACKGROUND: Nivolumab has shown improved survival in the treatment of advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. We assessed the safety and activity of combination nivolumab plus ipilimumab as first-line therapy for NSCLC. METHODS: The open-label, phase 1, multicohort study (CheckMate 012) cohorts reported here were enrolled at eight US academic centres. Eligible patients were aged 18 years or older with histologically or cytologically confirmed recurrent stage IIIb or stage IV, chemotherapy-naive NSCLC...
December 2, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27930644/immunotherapy-for-the-treatment-of-breast-cancer-checkpoint-blockade-cancer-vaccines-and-future-directions-in-combination-immunotherapy
#5
Heather L McArthur, David B Page
Immunotherapy encompasses both vaccines that direct immune responses to tumor-associated antigens, and checkpoint blocking antibodies that inhibit immune system suppression by targeting key pathways mediated by cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 (PD-1), and programmed death ligand 1 (PD-L1). Both of these approaches currently are being explored as potential strategies for the treatment of breast cancer. Recent studies suggest that immunotherapy is poised to change the therapeutic landscape for some breast cancers...
November 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27928788/-basic-and-translational-research-progress-of-gastrointestinal-neuroendocrine-neoplasmas
#6
Yuli Song, Xiaoyi Li, Tiantian Song, Guole Lin, Yuanjia Chen
Gastrointestinal neuroendocrine tumors are a group of highly heterogeneous tumors. Their incidences have increased in the Western countries as well as in Asia for years. In recent years, predominant progression has been made in the basic and translational studies on gastrointestinal neuroendocrine tumors. Gastric neuroendocrine neoplasmas are classified as four types: type I( occurs on the basis of autoimmune atrophic gastritis, type II( clinically manifests as multiple endocrine tumor type I( and Zollinger-Ellison syndrome, type III( is sporadic neuroendocrine neoplasmas, and type IIII( is neuroendocrine carcinoma...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27927966/tolerogenic-dendritic-cells-from-poorly-compensated-type-1-diabetes-patients-have-decreased-ability-to-induce-stable-antigen-specific-t-cell-hyporesponsiveness-and-generation-of-suppressive-regulatory-t-cells
#7
Klára Dáňová, Anna Grohová, Pavla Strnadová, David P Funda, Zdeněk Šumník, Jan Lebl, Ondřej Cinek, Štěpánka Průhová, Stanislava Koloušková, Barbora Obermannová, Lenka Petruželková, Anna Šedivá, Petra Fundová, Karsten Buschard, Radek Špíšek, Lenka Palová-Jelínková
Tolerogenic dendritic cells (tolDCs) may offer an interesting intervention strategy to re-establish Ag-specific tolerance in autoimmune diseases, including type 1 diabetes (T1D). T1D results from selective destruction of insulin-producing β cells leading to hyperglycemia that, in turn, specifically affects a patient's immune system. In this study, we prepared monocyte-derived tolDCs modulated by dexamethasone and vitamin D2 from 31 T1D patients with optimal glycemic control and 60 T1D patients with suboptimal glycemic control and assessed their tolerogenic properties in correlation with metabolic state of patients...
December 7, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27926522/il-10-expression-defines-an-immunosuppressive-dendritic-cell-population-induced-by-antitumor-therapeutic-vaccination
#8
Diana Llopiz, Marta Ruiz, Stefany Infante, Lorea Villanueva, Leyre Silva, Sandra Hervas-Stubbs, Diego Alignani, Elizabeth Guruceaga, Juan J Lasarte, Pablo Sarobe
Vaccination induces immunostimulatory signals that are often accompanied by regulatory mechanisms such as IL-10, which control T-cell activation and inhibit vaccine-dependent antitumor therapeutic effect. Here we characterized IL-10-producing cells in different tumor models treated with therapeutic vaccines. Although several cell subsets produced IL-10 irrespective of treatment, an early vaccine-dependent induction of IL-10 was detected in dendritic cells (DC). IL-10 production defined a DC population characterized by a poorly mature phenotype, lower expression of T-cell stimulating molecules and upregulation of PD-L1...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926518/higher-programmed-cell-death-1-ligand-1-pd-l1-mrna-level-in-clear-cell-renal-cell-carcinomas-is-associated-with-a-favorable-outcome-due-to-the-active-immune-responses-in-tumor-tissues
#9
Xiang-Hui Ning, Yan-Qing Gong, Shi-Ming He, Teng Li, Jiang-Yi Wang, Shuang-He Peng, Jin-Chao Chen, Jia-Yuan Liu, Nie-Nie Qi, Ying-Lu Guo, Kan Gong
Renal cell carcinoma is one of the most common urological tumors. The role of programmed cell death 1 ligand 1 (PD-L1) in renal cell carcinomas in predicting outcome of the patients is yet unclear. We analyzed the clinical and RNA-seq data of 522 kidney clear cell cancer, 259 kidney papillary cell carcinoma and 66 kidney chromophobe patients from The Cancer Genome Atlas (TCGA) database. In kidney clear cell cancer patients with high PD-L1 mRNA level and low PD-L1 mRNA level in tumors, the median overall survival periods were 45...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925176/pd-l1-expression-of-the-residual-tumor-serves-as-a-prognostic-marker-in-local-advanced-breast-cancer-after-neoadjuvant-chemotherapy
#10
Sheng Chen, Ruo-Xi Wang, Yin Liu, Wen-Tao Yang, Zhi-Ming Shao
This study sought to investigate the prevalence of programmed death ligand 1 (PD-L1) and its prognostic value in patients with residual tumors after neoadjuvant chemotherapy (NCT) for locally advanced breast cancer (LABC). A total of 309 patients considered as non-pathological complete responders (non-pCR) after NCT followed by mastectomy were selected. The expression of PD-L1 and tumor-infiltrating lymphocytes (TILs) in residual breast cancer cells was assessed by immunohistochemistry in surgical specimens...
December 7, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27924827/pd-1-pd-l-pathway-inhibits-m-tb-specific-cd4-t-cell-functions-and-phagocytosis-of-macrophages-in-active-tuberculosis
#11
Lei Shen, Yan Gao, Yuanyuan Liu, Bingyan Zhang, Qianqian Liu, Jing Wu, Lin Fan, Qinfang Ou, Wenhong Zhang, Lingyun Shao
The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924752/predictive-biomarkers-for-checkpoint-inhibitor-based-immunotherapy
#12
REVIEW
Geoffrey T Gibney, Louis M Weiner, Michael B Atkins
The clinical development of checkpoint inhibitor-based immunotherapy has ushered in an exciting era of anticancer therapy. Durable responses can be seen in patients with melanoma and other malignancies. Although monotherapy with PD-1 or PD-L1 agents are typically well tolerated, the risk of immune-related adverse events increases with combination regimens. The development of predictive biomarkers is needed to optimise patient benefit, minimise risk of toxicities, and guide combination approaches. The greatest focus has been on tumour-cell PD-L1 expression...
December 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27923550/treatment-design-and-rationale-for-a-randomized-trial-of-cisplatin-and-etoposide-plus-thoracic-radiotherapy-followed-by-nivolumab-or-placebo-for-locally-advanced-non-small-cell-lung-cancer-rtog-3505
#13
David E Gerber, James J Urbanic, Corey Langer, Chen Hu, I-Fen Chang, Bo Lu, Benjamin Movsas, Robert Jeraj, Walter J Curran, Jeffrey D Bradley
Radiation Therapy Oncology Group (RTOG) 3505 is a randomized phase 3 study of concurrent chemoradiation followed by immune checkpoint inhibitor therapy or placebo in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with surgically unresectable stage 3 NSCLC will receive thoracic radiotherapy to 60 Gy with concurrent cisplatin 50 mg/m(2) intravenously (I.V.) on days 1, 8, 29, and 36, and etoposide 50 mg/m(2) I.V. on days 1 to 5 and days 29 to 33. Between 4 and 12 weeks after completion of concurrent chemoradiation, eligible patients will be randomized to the anti-programmed death 1 (PD-1) monoclonal antibody nivolumab 240 mg I...
October 26, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27922697/regulation-of-pd-l1-expression-in-a-high-grade-invasive-human-oral-squamous-cell-carcinoma-microenvironment
#14
Mariko Hirai, Hiroko Kitahara, Yutaka Kobayashi, Koroku Kato, George Bou-Gharios, Hiroyuki Nakamura, Shuichi Kawashiri
Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients...
December 2, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27922481/pd-l1-assessment-for-targeted-therapy-testing-in-cancer-urgent-need-for-realistic-economic-and-practice-expectations
#15
Hadi Yaziji, Clive R Taylor
No abstract text is available yet for this article.
January 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27921410/downregulation-of-immunosuppressive-molecules-pd-1-and-pd-l1-but-not-pd-l2-in-the-patients-with-multiple-sclerosis
#16
Mohammad Reza Javan, Saeed Aslani, Mohammad Reza Zamani, Javad Rostamnejad, Milad Asadi, Mahdi Farhoodi, Mohammad Hossein Nicknam
Programmed cell death-1 (PD-1) and its ligands, PD-L1 and PD-L2, have been regarded as important immune system regulatory molecules. The aberrant expression of the molecules has been related to several autoimmune disorders. This study is aimed to assess the mRNA expression level of PD-1, PD-L1, and PD-L2 molecules in the peripheral blood mononuclear mells (PBMCs) from multiple sclerosis (MS) patients. PBMCs were isolated from the whole blood of 50 MS and 50 healthy individuals. Total RNA content of the leukocytes was extracted...
August 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27921007/long-term-response-to-nivolumab-and-acute-renal-failure-in-a-patient-with-metastatic-papillary-renal-cell-carcinoma-and-a-pd-l1-tumor-expression-increased-with-sunitinib-therapy-a-case-report
#17
Juan Ruiz-Bañobre, Urbano Anido, Ihab Abdulkader, José Antúnez-López, Rafael López-López, Jorge García-González
INTRODUCTION: Papillary renal cell carcinoma (PRCC), which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal cell carcinoma...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27920704/autoimmune-hemolytic-anemia-as-a-complication-of-nivolumab-therapy
#18
Amruth R Palla, Devin Kennedy, Hossain Mosharraf, Donald Doll
Recently, immunotherapeutic drugs, including PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab, avelumab), and CTLA4 inhibitors (ipiliumumab), have emerged as important additions to the armamentarium against certain malignancies and have been incorporated into therapeutic protocols for first-, second-, or third-line agents for these metastatic cancers. Immune checkpoint inhibitor nivolumab is currently FDA approved for the treatment of patients with metastatic malignant melanoma [Redman et al...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27920140/first-anti-pd-l1-drug-approved-for-nsclc
#19
(no author information available yet)
Based on the results of two large international randomized trials, the FDA approved the anti-PD-L1 agent atezolizumab in October. It is the first PD-L1 inhibitor approved for use in patients with metastatic non-small cell lung cancer that has advanced in spite of treatment with platinum-based chemotherapy.
December 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27919908/targeting-the-pd-1-pd-l1-axis-in-multiple-myeloma-a-dream-or-a-reality
#20
Jacalyn Rosenblatt, David Avigan
PD-1/PD-L1 pathway is a negative regulator of immune activation that is up-regulated in multiple myeloma and is a critical component of the immunosuppressive tumor microenvironment. Expression is increased in advanced disease and in the presence of bone marrow stromal cells. PD-1/PD-L1 blockade is associated with tumor regression in several malignancies but single agent activity is limited in myeloma patients. Combination therapy involving strategies to expand myeloma specific T cells and T cell activation via PD-1/PD-L1 blockade are currently being explored...
December 5, 2016: Blood
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