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PD-1 immune

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https://www.readbyqxmd.com/read/27913861/cxcl12-expression-and-pd-l1-expression-serve-as-prognostic-biomarkers-in-hcc-and-are-induced-by-hypoxia
#1
Alexander Semaan, Dimo Dietrich, Dominik Bergheim, Jörn Dietrich, Jörg C Kalff, Vittorio Branchi, Hanno Matthaei, Glen Kristiansen, Hans-Peter Fischer, Diane Goltz
Anti-PD-1 treatment increases anti-tumour immune responses in animal models of hepatocellular carcinoma (HCC). Sorafenib, the mainstay of treatment of HCC patients, however, leads to tumour hypoxia and thereby abrogates the efficacy of anti-PD-1 treatment. This served as a rationale to implement CXCR4 inhibition as adjunct to sorafenib and anti-PD-1 treatment in murine HCC models. We studied the relationship between tumour hypoxia, PD-L1 and CXCL12 expression in human HCC, aiming to test the rationale for triple therapy combining sorafenib, PD-1 immune checkpoint inhibitors and CXCR4 inhibitors...
December 2, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27913506/checkpoint-inhibition-and-cellular-immunotherapy-in-lymphoma
#2
Premal Lulla, Helen E Heslop
Hodgkin and non-Hodgkin lymphoma are both good targets for immunotherapy, as they are accessible to antibodies and cell-based immunotherapy, express costimulatory molecules, and express lineage-restricted, viral, and unique tumor antigens. Blockade of the programmed-death 1 (PD-1) immune checkpoint has produced very encouraging response rates in patients with Hodgkin lymphoma, whereas adoptive transfer of Epstein-Barr Virus (EBV)-specific T cells has shown clinical activity in patients with posttransplant lymphoma and other EBV-associated lymphomas...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913228/pd-l1-immunohistochemistry-assays-for-lung-cancer-results-from-phase-1-of-the-blueprint-pd-l1-ihc-assay-comparison-project
#3
Fred R Hirsch, Abigail McElhinny, Dave Stanforth, James Ranger-Moore, Malinka Jansson, Karina Kulangara, William Richardson, Penny Towne, Debra Hanks, Bharathi Vennapusa, Amita Mistry, Rasika Kalamegham, Steve Averbuch, James Novotny, Eric Rubin, Kenneth Emancipator, Ian McCaffery, J Andrew Williams, Jill Walker, John Longshore, Ming S Tsao, Keith M Kerr
BACKGROUND: The "Blueprint PD-L1 IHC Assay Comparison Project" is an industrial-academic collaborative partnership to provide information on the analytical and clinical comparability of four PD-L1 IHC assays used in clinical trials. METHODS: 39 NSCLC tumors were stained with four PD-L1 IHC assays (22C3, 28-8, SP 142 and SP 263) as used in the clinical trials. Three experts in interpreting their respective assays independently evaluated the percentages of tumor and immune cells staining positive at any intensity...
November 29, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27912829/immunotherapy-in-lung-cancer
#4
REVIEW
Lingling Du, Roy S Herbst, Daniel Morgensztern
The treatment of patients with good performance status and advanced stage non-small cell lung cancer has been based on the use of first-line platinum-based doublet and second-line docetaxel. Immunotherapy represents a new therapeutic approach with the potential for prolonged benefit. Although the vaccines studied have not shown benefit in patients with non-small cell lung cancer, immune checkpoint inhibitors against the PD-1/PD-L1 axis showed increased overall survival compared with docetaxel in randomized clinical trials, which led to the approval of nivolumab and pembrolizumab...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912781/an-immune-stratification-reveals-a-subset-of-pd-1-lag-3-double-positive-triple-negative-breast-cancers
#5
Giulia Bottai, Carlotta Raschioni, Agnese Losurdo, Luca Di Tommaso, Corrado Tinterri, Rosalba Torrisi, Jorge S Reis-Filho, Massimo Roncalli, Christos Sotiriou, Armando Santoro, Alberto Mantovani, Sherene Loi, Libero Santarpia
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259)...
December 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#6
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910704/the-safety-of-nivolumab-for-the-treatment-of-advanced-non-small-cell-lung-cancer
#7
Giulio Metro, Biagio Ricciuti, Marta Brambilla, Sara Baglivo, Irene Soli, Elisa Minenza, Giulia Costanza Leonardi, Alessandro D'Arpino, Daniela Colabrese, Marco Tazza, Daniela Zicari, Vincenzo Minotti, Rita Chiari
Immune checkpoint blockaders (ICBs) act by unbalancing the immune system, thus favoring the development of an immune-mediated antitumor effect. ICBs targeting the programmed cell death receptor-1 (PD-1) have recently been investigated in a number of advanced tumors, including non-small cell lung cancer (NSCLC). Nivolumab, a fully human IgG4 kappa directed against PD-1, has been the first ICB to be approved for second-line treatment of advanced NSCLC. Areas covered: In this review we focus on the clinical development of nivolumab for the treatment of advanced NSCLC, with an emphasis on its safety profile...
December 2, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27909177/editorial-blockade-of-pd-1-and-pd-l1-restores-defective-innate-immune-responses-in-leukocytes-from-septic-humans
#8
EDITORIAL
Peter A Ward, Fatemeh Fattahi
No abstract text is available yet for this article.
December 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27908252/the-combination-of-new-immunotherapy-and-radiotherapy-a-new-potential-treatment-for-locally-advanced-non-small-cell-lung-cancer
#9
Paola Claudia Sacco, Paolo Maione, Cesare Guida, Cesare Gridelli
Lung cancer is the main reason of cancer death worldwide. About 30% of non-small-cell lung cancer (NSCLC) cases are diagnosed with locally advanced disease (stage III). This is a mixed population including patients who have far more extensive and bulky disease than others. Management of these patients continue to be a challenge; frequently, patients have both local recurrence and distant metastases in this stage and the prognosis is very poor with a 5-year overall survival estimated between 3% and 7% for inoperable disease...
December 1, 2016: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/27903674/atezolizumab-a-pd-l1-blocking-antibody-for-bladder-cancer
#10
Brant A Inman, Thomas A Longo, Sundhar Ramalingam, Michael R Harrison
Atezolizumab (Tecentriq™, MPDL3280A) is an FcγR-binding deficient, fully humanized, IgG1 monoclonal antibody designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironement and consequently increases T cell mediated immunity against the tumor. Atezolizumab has been FDA-approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase 2 trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27903604/what-does-pd-l1-positive-or-negative-mean
#11
Antoni Ribas, Siwen Hu-Lieskovan
Expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) is used to select patients and analyze responses to anti-PD-1/L1 antibodies. The expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence or absence. PD-L1 positivity may be a result of genetic events leading to constitutive PD-L1 expression on cancer cells or inducible PD-L1 expression on cancer cells and noncancer cells in response to a T cell infiltrate. A tumor may be PD-L1 negative because it has no T cell infiltrate, which may be reversed with an immune response...
November 30, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27895917/validation-of-biomarkers-to-predict-response-to-immunotherapy-in-cancer-volume-i-pre-analytical-and-analytical-validation
#12
REVIEW
Giuseppe V Masucci, Alessandra Cesano, Rachael Hawtin, Sylvia Janetzki, Jenny Zhang, Ilan Kirsch, Kevin K Dobbin, John Alvarez, Paul B Robbins, Senthamil R Selvan, Howard Z Streicher, Lisa H Butterfield, Magdalena Thurin
Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, there have been many clinical successes using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). Despite demonstrated successes in a variety of malignancies, responses only typically occur in a minority of patients in any given histology. Additionally, treatment is associated with inflammatory toxicity and high cost...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27894751/polymerase-%C3%AE%C2%B5-pole-ultra-mutation-in-uterine-tumors-correlates-with-t-lymphocyte-infiltration-and-increased-resistance-to-platinum-based-chemotherapy-in-vitro
#13
Stefania Bellone, Eliana Bignotti, Silvia Lonardi, Francesca Ferrari, Floriana Centritto, Alice Masserdotti, Francesca Pettinella, Jonathan Black, Gulden Menderes, Gary Altwerger, Pei Hui, Salvatore Lopez, Christopher de Haydu, Elena Bonazzoli, Federica Predolini, Luca Zammataro, Emiliano Cocco, Federico Ferrari, Antonella Ravaggi, Chiara Romani, Fabio Facchetti, Enrico Sartori, Franco E Odicino, Dan-Arin Silasi, Babak Litkouhi, Elena Ratner, Masoud Azodi, Peter E Schwartz, Alessandro D Santin
OBJECTIVE: Up to 12% of all endometrial-carcinomas (EC) harbor DNA-polymerase-ε-(POLE) mutations. It is currently unknown whether the favorable prognosis of POLE-mutated EC is derived from their low metastatic capability, extraordinary number of somatic mutations thus imparting immunogenicity, or a high sensitivity to chemotherapy. METHODS: Polymerase-chain-reaction-amplification and Sanger-sequencing were used to test for POLE exonuclease-domain-mutations (exons 9-14) 131 EC...
November 25, 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27894673/treatment-related-death-in-cancer-patients-treated-with-immune-checkpoint-inhibitors-a-systematic-review-and-meta-analysis
#14
O Abdel-Rahman, D Helbling, J Schmidt, U Petrausch, A Giryes, A Mehrabi, O Schöb, M Mannhart, H Oweira
AIMS: We carried out a meta-analysis to determine the risk of treatment-related death associated with immune checkpoint inhibitor use in cancer patients. MATERIALS AND METHODS: We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, pembrolizumab; nivolumab; tremelimumab and atezolizumab...
November 25, 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/27893699/nivolumab-induced-severe-akathisia-in-an-advanced-lung-cancer-patient
#15
Jiro Abe, Taku Sato, Ryota Tanaka, Toshimasa Okazaki, Satomi Takahashi
BACKGROUND Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed for cancer immunotherapy. In the clinical trials of nivolumab, its adverse effects were reported to be less likely than those of conventional anti-cancer agents; however, after practical clinical distribution, it has come to be known that nivolumab induces various immune-related adverse events. CASE REPORT A 58-year-old male with a recurrence of lung adenocarcinoma was treated with nivolumab. Only four days after the initial administration of nivolumab, the patient presented with unbearable restlessness and distress that was resistant to all therapeutic agents used, and it gradually became worse...
November 23, 2016: American Journal of Case Reports
https://www.readbyqxmd.com/read/27889994/pd-1-pd-ls-a-new-target-for-regulating-the-immunopathogenesis-in-central-nervous-system-disorders
#16
Jie Wu, Zhengquan Yu, Gang Chen
The central nervous system (CNS) was traditionally thought to tolerate inflammatory responses. However, CNS is not completely immune-privileged in recent researches. These responses including Microglia and macrophage activation and peripheral immune cells infiltration have been founded successively. Thus, the traditional view of the adult brain as an immune-privileged organ has been changed. Increasing evidence indicated that the PD-1(programmed cell death-1)/PD-Ls signal pathway plays an important role in regulating the immunopathogenesis of brain following injury...
November 23, 2016: Current Drug Delivery
https://www.readbyqxmd.com/read/27887569/immune-modulation-of-cd4-cd25-regulatory-t-cells-by-zoledronic-acid
#17
Hsien Liu, Shih-Han Wang, Shin-Cheh Chen, Ching-Ying Chen, Jo-Lin Lo, Tsun-Mei Lin
BACKGROUND: CD4(+)CD25(+) regulatory T (Treg) cells suppress tumor immunity by inhibiting immune cells. Manipulation of Treg cells represents a new strategy for cancer treatment. Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, inhibits the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) on osteoblasts to inhibit osteoclastogenesis. In a mouse model of bisphosphonate-related osteonecrosis of the jaw, administration of ZA suppressed Treg-cell activity and activated inflammatory Th17 cells...
November 25, 2016: BMC Immunology
https://www.readbyqxmd.com/read/27886124/advances-in-cancer-immunotherapy-in-solid-tumors
#18
REVIEW
Smitha Menon, Sarah Shin, Grace Dy
Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses...
November 24, 2016: Cancers
https://www.readbyqxmd.com/read/27882863/porphyromonas-gingivalis-suppresses-adaptive-immunity-in-periodontitis-atherosclerosis-and-alzheimer-s-disease
#19
REVIEW
Ingar Olsen, Martin A Taubman, Sim K Singhrao
Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer's disease (AD). Although P. gingivalis has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host's adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions...
2016: Journal of Oral Microbiology
https://www.readbyqxmd.com/read/27881581/nivolumab-in-the-treatment-of-hodgkin-lymphoma
#20
Stephen M Ansell
Despite an extensive immune infiltrate that is recruited to the tumor by malignant Reed Sternberg cells in Hodgkin lymphoma, the antitumor immune response is ineffective and unable to eradicate the malignant cells. The ineffective immune response is in part due to PD-1 signaling that renders intratumoral immune cells anergic. Reed Sternberg cells have been shown to upregulate expression of the PD-1 ligands, PD-L1 and PD-L2, due to either genetic alterations at chromosome 9p24.1 or Epstein Barr virus infection, and these ligands suppress the function of PD-1+ intratumoral T-cells...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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