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https://www.readbyqxmd.com/read/28932634/pd1-positive-tumor-infiltrating-lymphocytes-are-associated-with-poor-clinical-outcome-after-pulmonary-metastasectomy-for-colorectal-cancer
#1
Dagmar Kollmann, Thomas Schweiger, Stefan Schwarz, Desislava Ignatova, Yun-Tsan Chang, Gerrit Lewik, Sebastian F Schoppmann, Wolfram Hoetzenecker, Walter Klepetko, Emmanuella Guenova, Konrad Hoetzenecker
Pulmonary metastasectomy (PM) is routinely performed in colorectal cancer (CRC) patients with oligometastatic spreading to the lungs. Patients with an aggressive tumor phenotype should be excluded from PM, since its benefit is outweighed by early tumor recurrence and impaired prognosis. Expression of PD-1 and its ligands are prognostic factors in a variety of primary tumors. However, their impact on patients' outcome in the setting of PM for CRC has not been evaluated before. 53 CRC patients with pulmonary metastases receiving PM with curative intent were included in this study...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28915646/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#2
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4(th) leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893733/topological-analysis-reveals-a-pd-l1-associated-microenvironmental-niche-for-reed-sternberg-cells-in-hodgkin-lymphoma
#3
Christopher D Carey, Daniel Gusenleitner, Mikel Lipschitz, Margaretha G M Roemer, Edward C Stack, Evisa Gjini, Xihao Hu, Robert Redd, Gordon J Freeman, Donna Neuberg, F Stephen Hodi, Xiaole Shirley Liu, Margaret A Shipp, Scott J Rodig
Signaling between programmed cell death protein 1 (PD-1) and the programmed cell death -1 ligands (PD-1 ligands, PD-L1, PD-L2) is essential for malignant Hodgkin Reed-Sternberg (HRS) cells to evade anti-tumor immunity in classical Hodgkin lymphoma (cHL). Copy number alterations of 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2) contribute to robust PD-L1 and PD-L2 expression by HRS cells. PD-L1 is also expressed by non-malignant tumor-associated macrophages (TAMs) but the relationships between PD-L1+ HRS cells, PD-L1+ TAMs, and PD-1+ T-cells remain undefined...
September 11, 2017: Blood
https://www.readbyqxmd.com/read/28892775/challenges-and-perspectives-in-the-immunotherapy-of-hodgkin-lymphoma
#4
REVIEW
Jean-Marie Michot, Julien Lazarovici, David Ghez, Alina Danu, Christophe Fermé, Amélie Bigorgne, Vincent Ribrag, Aurélien Marabelle, Sandrine Aspeslagh
Hodgkin lymphoma (HL) was one of the first few cancers to be cured first with radiotherapy alone and then with a combination of chemotherapy and radiotherapy. Around 80% of the patients with HL will be cured by first-line therapy. However, the ionising radiation not only produces cytotoxicity but also induces alterations in the microenvironment, and patients often struggle with the long-term consequences of these treatments, such as cardiovascular disorders, lung diseases and secondary malignancies. Hence, it is essential to improve treatments while avoiding delayed side-effects...
September 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28881780/pd-l1-a-novel-prognostic-biomarker-in-head-and-neck-squamous-cell-carcinoma
#5
Tim Müller, Martin Braun, Dimo Dietrich, Seher Aktekin, Simon Höft, Glen Kristiansen, Friederike Göke, Andreas Schröck, Johannes Brägelmann, Stefanie A E Held, Friedrich Bootz, Peter Brossart
BACKGROUND: The PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28866656/immune-checkpoint-inhibitors-in-cancer-therapy
#6
Eika S Webb, Peng Liu, Renato Baleeiro, Nicholas R Lemoine, Ming Yuan, Yao-He Wang
In recent years immune checkpoint inhibitors have garnered attention as being one of the most promising types of immunotherapy on the horizon. There has been particular focus on the immune checkpoint molecules, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) which have been shown to have potent immunomodulatory effects through their function as negative regulators of T cell activation. CTLA-4, through engagement with its ligands B7-1 (CD80) and B7-2 (CD86), plays a pivotal role in attenuating the activation of naïve and memory T cells...
September 3, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28865147/differential-regulation-of-pd-1-and-its-ligands-in-allergic-asthma
#7
Kai Bratke, Linda Fritz, Fabian Nokodian, Kristina Geißler, Katharina Garbe, Marek Lommatzsch, J Christian Virchow
BACKGROUND: Targeting PD-1/PD-1 ligand signalling is an established treatment option for cancer. The role of these molecules in allergic asthma has been investigated in several mouse studies yielding conflicting results. However, human studies investigating the expression and regulation of PD-1 and its ligands in allergic inflammation are lacking. OBJECTIVE: To analyse the expression and regulation of PD-1 and its ligands in human allergic asthma. METHODS: The well-established human asthma model of segmental allergen challenge (SAC) was used to analyse the regulation of PD-1 and its ligands PD-L1 and PD-L2 on T lymphocytes and dendritic cells by flow cytometry...
September 2, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28864476/recurrent-tumor-cell-intrinsic-and-extrinsic-alterations-during-mapki-induced-melanoma-regression-and-early-adaptation
#8
Chunying Song, Marco Piva, Lu Sun, Aayoung Hong, Gatien Moriceau, Xiangju Kong, Hong Zhang, Shirley Lomeli, Jin Qian, Clarissa C Yu, Robert Damoiseaux, Mark C Kelley, Kimberly B Dahlman, Philip O Scumpia, Jeffrey A Sosman, Douglas B Johnson, Antoni Ribas, Willy Hugo, Roger S Lo
Treatment of advanced V600BRAF mutant melanoma using a BRAF inhibitor (BRAFi) or its combination with a MEKi typically elicits partial responses. We compared the transcriptomes of patient-derived tumors regressing on MAPKi therapy against MAPKi-induced temporal transcriptomic states in human melanoma cell lines or murine melanoma in immune-competent mice. Despite heterogeneous dynamics of clinical tumor regression, residual tumors displayed highly recurrent transcriptomic alterations and enriched processes, which were also observed in MAPKi-selected cell lines (implying tumor cell-intrinsic reprogramming) or in bulk mouse tumors (and the CD45-negative or -positive fractions,, implying tumor cell-intrinsic or stromal/immune alterations, respectively)...
September 1, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28842748/pd-l1-expression-correlates-with-vegf-and-microvessel-density-in-patients-with-uniformly-treated-classical-hodgkin-lymphoma
#9
Young Wha Koh, Jae-Ho Han, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh
Recent studies have reported the associations between programmed death-ligand 1 (PD-L1) or PD-L2/PD-1 pathways and pro-angiogenic genes including hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) in several malignancies. However, no study has examined the relationship or prognostic implication of PD-L1, PD-L2, PD-1, VEGF expression, and microvessel density (MVD) in classical Hodgkin lymphoma (cHL) patients. Diagnostic tissues from 109 patients with doxorubicin, bleomycin, vinblastine, and dacarbazine-treated cHL were evaluated retrospectively by immunohistochemical analysis for PD-L1, PD-L2, PD-1, VEGF expression, and for CD31 expression as a measure of MVD...
August 25, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28819821/anti-pd-1-antibodies-as-a-therapeutic-strategy-in-classical-hodgkin-lymphoma
#10
REVIEW
Michael D Jain, John Kuruvilla
Classical Hodgkin lymphoma (cHL) is defined by malignant Reed-Sternberg (RS) cells that recruit non-malignant immune cells into a supportive tumour microenvironment. In cHL, this is driven, in part, by genomic alterations of the 9p24.1 locus encoding the immune checkpoint ligands PD-L1 and PD-L2. Therapeutic anti-PD-1 antibodies have been developed that competitively inhibit the interaction between PD-1 and its ligands. Clinical trials of anti-PD-1 antibodies in cHL demonstrate high overall response rates but relapses still occur and new clinical challenges exist for toxicity management and response assessment...
August 17, 2017: Drugs
https://www.readbyqxmd.com/read/28812434/-pemetrexed-sildenafil-via-autophagy-dependent-hdac-down-regulation-enhances-the-immunotherapy-response-of-nsclc-cells
#11
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
Pemetrexed is an approved therapeutic in NSCLC and ovarian cancer. Our studies focused on the ability of [pemetrexed + sildenafil] exposure to alter the immunogenicity of lung and ovarian cancer cells. Treatment of lung and ovarian cancer cells with [pemetrexed + sildenafil] in vitro rapidly reduced the expression of PD-L1, PD-L2 and ornithine decarboxylase (ODC), and increased the expression of Class I MHCA. In a cell-specific fashion, some cells also released the immunogenic nuclear protein HMGB1 into the extracellular environment...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28811964/pd-l2-expression-in-colorectal-cancer-independent-prognostic-effect-and-targetability-by-deglycosylation
#12
Huanbin Wang, Han Yao, Chushu Li, Lunxi Liang, Yao Zhang, Hubing Shi, Chongzhi Zhou, Yingxuan Chen, Jing-Yuan Fang, Jie Xu
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28803798/radiosynthesis-and-preclinical-pet-evaluation-of-89-zr-nivolumab-bms-936558-in-healthy-non-human-primates
#13
Erin L Cole, Joonyoung Kim, David J Donnelly, R Adam Smith, Daniel Cohen, Virginie Lafont, Paul E Morin, Richard Y-C Huang, Patrick L Chow, Wendy Hayes, Samuel Bonacorsi
Cancer immunotherapy, unlike traditional cytotoxic chemotherapeutic treatments, engages the immune system to identify cancer cells and stimulate immune responses. The Programmed Death-1 (PD-1) protein is an immunoinhibitory receptor expressed by activated cytotoxic T-lymphocytes (CTL) that seek out and destroy cancer cells. Multiple cancer types express and upregulate the Programmed Death-Ligand 1 (PD-L1) and 2 (PD-L2) which bind to PD-1 as an immune escape mechanism. Nivolumab is a fully human IgG4 anti-PD-1 monoclonal antibody (mAb) approved for treatment of multiple cancer types...
August 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28777458/increased-expression-of-pd-l1-and-pd-l2-in-dermal-fibroblasts-from-alopecia-areata-mice
#14
Yunyuan Li, Ruhi T Kilani, Mohammadreza Pakyari, Gigi Leung, Layla Nabai, Aziz Ghahary
Alopecia areata (AA) is a common autoimmune disorder affecting millions of people worldwide, which manifests as a sudden, non-scarring hair loss. The expression of a pro-inflammatory cytokine, interferon-gamma (INF-γ), has been well established to be involved in the development of AA. As IFN-γ and other cytokines are also known to up-regulate programmed cell death ligand 1 and 2 (PD-L1 and PD-L2), which both negatively control immune responses, we asked whether or not a high number of infiltrated T cells, seen in AA lesions, can modulate the expression of PD-L1 and PD-L2 in skin cells...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28768724/pd-l2-regulates-b-1-cell-antibody-production-against-phosphorylcholine-through-an-il-5-dependent-mechanism
#15
Jerome T McKay, Marcela A Haro, Christina A Daly, Rama D Yammani, Bing Pang, W Edward Swords, Karen M Haas
B-1 cells produce natural Abs which provide an integral first line of defense against pathogens while also performing important homeostatic housekeeping functions. In this study, we demonstrate that programmed cell death 1 ligand 2 (PD-L2) regulates the production of natural Abs against phosphorylcholine (PC). Naive PD-L2-deficient (PD-L2(-/-)) mice produced significantly more PC-reactive IgM and IgA. This afforded PD-L2(-/-) mice with selectively enhanced protection against PC-expressing nontypeable Haemophilus influenzae, but not PC-negative nontypeable Haemophilus influenzae, relative to wild-type mice...
September 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28768162/structural-biology-of-the-immune-checkpoint-receptor-pd-1-and-its-ligands-pd-l1-pd-l2
#16
REVIEW
Krzysztof M Zak, Przemyslaw Grudnik, Katarzyna Magiera, Alexander Dömling, Grzegorz Dubin, Tad A Holak
Cancer cells can avoid and suppress immune responses through activation of inhibitory immune checkpoint proteins, such as PD-1, PD-L1, and CTLA-4. Blocking the activities of these proteins with monoclonal antibodies, and thus restoring T cell function, has delivered breakthrough therapies against cancer. In this review, we describe the latest work on structural characterization of the checkpoint proteins, their interactions with cognate ligands and with therapeutic antibodies. Structures of the extracellular portions of these proteins reveal that they all have a similar modular structure, composed of small domains similar in topology to the domains found in antibodies...
August 1, 2017: Structure
https://www.readbyqxmd.com/read/28767423/pd-1-and-pd-l1-co-expression-predicts-favorable-prognosis-in-gastric-cancer
#17
Yanhua Wu, Donghui Cao, Limei Qu, Xueyuan Cao, Zhifang Jia, Tiancheng Zhao, Quan Wang, Jing Jiang
While the prognosis of gastric cancer (GC) remains poor, PD-1 and PD-L1/L2 are promising prognostic biomarkers. We evaluated PD-1 and PD-L1/L2 expression in tumor cells (TCs) and tumor-infiltrating immune cells (TIICs). We determined the Helicobacter pylori (Hp) and Epstein-Barr virus (EBV) infection status in a GC cohort (n=340), then analyzed the relationship between the expression of PD-1, PD-L1/L2 and GC prognosis. We found that PD-1, PD-L1, and PD-L2 mRNA levels were up-regulated in GC tissues, and were positively correlated with one another (P=0...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28754154/prognostic-value-of-programmed-death-1-programmed-death-ligand-1-programmed-death-ligand-2-expression-and-cd8-t-cell-density-in-primary-tumors-and-metastatic-lymph-nodes-from-patients-with-stage-t1-4n-m0-gastric-adenocarcinoma
#18
Yuan Gao, Su Li, Dazhi Xu, Shangxiang Chen, Yuchen Cai, Wenqi Jiang, Xinke Zhang, Jin Sun, Kefeng Wang, Boyang Chang, Fenghua Wang, Minghuang Hong
BACKGROUND: Anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra- and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy. This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules...
July 29, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28753790/positive-pelvic-lymph-nodes-in-prostate-cancer-harbor-immune-suppressor-cells-to-impair-tumor-reactive-t-cells
#19
Vidit Sharma, Haidong Dong, Eugene Kwon, R Jeffrey Karnes
The impact of prostate cancer (PCa) metastases on pelvic lymph nodes in local antitumor immunity remains unknown. We prospectively enrolled ten hormone therapy-naïve men undergoing salvage pelvic lymph node dissection (sPLND) and analyzed their peripheral blood (PB) and positive pelvic lymph nodes (PPLNs) with PCa metastases for tumor-reactive CD8(+) T cells and myeloid-derived suppressor cells (MDSCs) using flow cytometry. MDSCs were stratified into CD14(+) monocytic and CD14(-) granulocytic types. PD-L1/2 expression was also analyzed for MDSCs...
September 21, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28752839/development-and-validation-of-a-novel-clinical-fluorescence-in-situ-hybridization-assay-to-detect-jak2-and-pd-l1-amplification-a-fluorescence-in-situ-hybridization-assay-for-jak2-and-pd-l1-amplification
#20
Meixuan Chen, Mariacarla Andreozzi, Barbara Pockaj, Michael T Barrett, Idris Tolgay Ocal, Ann E McCullough, Maria E Linnaus, James M Chang, Jennifer H Yearley, Lakshmanan Annamalai, Karen S Anderson
The amplification of chromosome 9p24.1 encoding PD-L1, PD-L2, and JAK2 has been reported in multiple types of cancer and is associated with poor outcome, upregulation of PD-L1, and activation of the JAK/STAT pathway. We have developed a novel fluorescence in situ hybridization assay which combines 3 probes mapping to 9p24.1 with a commercial chromosome 9 centromere (CEN9) probe for detection of the JAK2/9p24.1 amplification. JAK2 fluorescence in situ hybridization was compared with array-based comparative genomic hybridization in 34 samples of triple negative breast cancer tumor...
July 28, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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