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PDL1

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https://www.readbyqxmd.com/read/29434933/pd-l1-expression-is-associated-with-p16-ink4a-expression-in-non-oropharyngeal-head-and-neck-squamous-cell-carcinoma
#1
San-Chi Chen, Peter Mu-Hsin Chang, Hsiao-Jung Wang, Shyh-Kuan Tai, Pen-Yuan Chu, Muh-Hwa Yang
PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD-L1 expression in non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non-OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin-embedded non-OPHNSCC samples obtained from patients were constructed, and PD-L1 and p16 INK4A expression were determined using immunohistochemistry...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434371/kidney-cancer-pdl1-as-a-biomarker-in-high-risk-rcc
#2
Rebecca Kelsey
No abstract text is available yet for this article.
February 13, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29434366/potentiating-prostate-cancer-immunotherapy-with-oncolytic-viruses
#3
REVIEW
Patrick Lee, Shashi Gujar
The clinical effectiveness of immunotherapies for prostate cancer remains subpar compared with that for other cancers. The goal of most immunotherapies is the activation of immune effectors, such as T cells and natural killer cells, as the presence of these activated mediators positively correlates with patient outcomes. Clinical evidence shows that prostate cancer is immunogenic, accessible to the immune system, and can be targeted by antitumour immune responses. However, owing to the detrimental effects of prostate-cancer-associated immunosuppression, even the newest immunotherapeutic approaches fail to initiate the clinically desired antitumour immune reaction...
February 13, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29428449/pd-1-pd-l1-checkpoint-in-hematological-malignancies
#4
REVIEW
O Annibali, A Crescenzi, V Tomarchio, A Pagano, A Bianchi, A Grifoni, G Avvisati
Programmed cell death protein 1 (PD-1), is a cell surface receptor with an important role in down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. PD-1/PDL1 axis represents a checkpoint to control immune responses and it is often used as a mechanism of immune escaping by cancers and infectious diseases. Many data demonstrate its important role in solid tumors and report emerging evidences in lymphoproliferative disorders. In this review, we summarized the available data on the role of PD-1/PD-L1 checkpoint in lymphoproliferative diseases and the therapeutics use of monoclonal blocking antibodies...
January 31, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29427592/establishment-of-engineered-cell-based-assays-mediating-lag3-and-pd1-immune-suppression-enables-potency-measurement-of-blocking-antibodies-and-assessment-of-signal-transduction
#5
Bhagyashree Bhagwat, Holly Cherwinski, Manjiri Sathe, Wolfgang Seghezzi, Terrill K McClanahan, Rene de Waal Malefyt, Aarron Willingham
LAG3 is an important regulator of T cell homeostasis and studies in mouse tumor models have demonstrated that simultaneously antagonizing LAG3 and PD1 can augment tumor-specific T cell responses and induce tumor rejection. The combined use of LAG3 antagonist antibodies with established anti-PD1 therapies is currently being evaluated in human clinical trials. A functional assay for human LAG3 was developed by co-culture of a Jurkat T-cell lymphoma line overexpressing LAG3 with a Raji B-cell lymphoma line in the presence of staphylococcal enterotoxins...
February 7, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29399401/a-safe-and-highly-efficient-tumor-targeted-type-i-interferon-immunotherapy-depends-on-the-tumor-microenvironment
#6
Anje Cauwels, Sandra Van Lint, Geneviève Garcin, Jennyfer Bultinck, Franciane Paul, Sarah Gerlo, José Van der Heyden, Yann Bordat, Dominiek Catteeuw, Lode De Cauwer, Elke Rogge, Annick Verhee, Gilles Uzé, Jan Tavernier
Despite approval for the treatment of various malignancies, clinical application of cytokines such as type I interferon (IFN) is severely impeded by their systemic toxicity. AcTakines (Activity-on-Target cytokines) are optimized immunocytokines that, when injected in mice, only reveal their activity upon cell-specific impact. We here show that type I IFN-derived AcTaferon targeted to the tumor displays strong antitumor activity without any associated toxicity, in contrast with wild type IFN. Treatment with CD20-targeted AcTaferon of CD20+ lymphoma tumors or melanoma tumors engineered to be CD20+, drastically reduced tumor growth...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399387/analysis-of-pd1-pdl1-pdl2-expression-and-t-cells-infiltration-in-1014-gastric-cancer-patients
#7
Xiaofang Xing, Jianping Guo, Xianzi Wen, Guangyu Ding, Bo Li, Bin Dong, Qin Feng, Shen Li, Jian Zhang, Xiaojing Cheng, Ting Guo, Hong Du, Ying Hu, Xiaohong Wang, Lin Li, Qingda Li, Meng Xie, Liting Li, Xiangyu Gao, Fei Shan, Ziyu Li, Xiaomin Ying, Tao Zhou, Jiping Wang, Jiafu Ji
Although immune checkpoint blockade have demonstrated promising results, their effects on gastric cancer (GC) are under investigation. Understanding the clinical significance of PD1 and its ligands' expression, together with T cell infiltration might provide clues for biomarkers screening in GC immunotherapy. Immunohistochemistry were performed on a tissue microarray including 1,014 GC specimens using PD1, PDL1 and PDL2 antibodies. T cell markers CD3 and CD8 were also stained and quantified by automated image analysis...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29391205/primary-and-metastatic-brain-cancer-genomics-and-emerging-biomarkers-for-immunomodulatory-cancer-treatment
#8
REVIEW
F Passiglia, C Caglevic, E Giovannetti, J A Pinto, P Manca, S Taverna, A Listì, I Gil-Bazo, L E Raez, A Russo, C Rolfo
Recent studies with immunomodulatory agents targeting both cytotoxic T-lymphocyte protein 4 (CTLA4) and programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) have shown to be very effective in several cancers revealing an unexpected great activity in patients with both primary and metastatic brain tumors. Combining anti-CTLA4 and anti-PD1 agents as upfront systemic therapy has revealed to further increase the clinical benefit observed with single agent, even at cost of higher toxicity. Since the brain is an immunological specialized area it's crucial to establish the specific composition of the brain tumors' microenvironment in order to predict the potential activity of immunomodulatory agents...
January 31, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29386574/development-of-an-immune-pathology-informed-radiomics-model-for-non-small-cell-lung-cancer
#9
Chad Tang, Brian Hobbs, Ahmed Amer, Xiao Li, Carmen Behrens, Jaime Rodriguez Canales, Edwin Parra Cuentas, Pamela Villalobos, David Fried, Joe Y Chang, David S Hong, James W Welsh, Boris Sepesi, Laurence Court, Ignacio I Wistuba, Eugene J Koay
With increasing use of immunotherapy agents, pretreatment strategies for identifying responders and non-responders is useful for appropriate treatment assignment. We hypothesize that the local immune micro-environment of NSCLC is associated with patient outcomes and that these local immune features exhibit distinct radiologic characteristics discernible by quantitative imaging metrics. We assembled two cohorts of NSCLC patients treated with definitive surgical resection and extracted quantitative parameters from pretreatment CT imaging...
January 31, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29383101/cxcr2-mdscs-promote-breast-cancer-progression-by-inducing-emt-and-activated-t-cell-exhaustion
#10
Ha Zhu, Yan Gu, Yiquan Xue, Ming Yuan, Xuetao Cao, Qiuyan Liu
Although myeloid-derived suppressor cells (MDSCs) have been demonstrated to contribute to tumor initiation, progression and metastasis, however, which MDSC subsets are preferentially expanded and activated, and what's the key molecular mechanism responsible for specific MDSC subsets in promoting tumor progression need to be fully addressed. Here we identify that Ly6GmiLy6CloCD11b+CXCR2+ subpopulation (named CXCR2+ MDSCs) are predominately expanded and recruited in systemic and local tumor microenvironment during breast cancer progression and metastasis...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29367423/chemotherapy-induces-enrichment-of-cd47-cd73-pdl1-immune-evasive-triple-negative-breast-cancer-cells
#11
Debangshu Samanta, Youngrok Park, Xuhao Ni, Huili Li, Cynthia A Zahnow, Edward Gabrielson, Fan Pan, Gregg L Semenza
Triple-negative breast cancer (TNBC) is treated with cytotoxic chemotherapy and is often characterized by early relapse and metastasis. To form a secondary (recurrent and/or metastatic) tumor, a breast cancer cell must evade the innate and adaptive immune systems. CD47 enables cancer cells to evade killing by macrophages, whereas CD73 and PDL1 mediate independent mechanisms of evasion of cytotoxic T lymphocytes. Here, we report that treatment of human or murine TNBC cells with carboplatin, doxorubicin, gemcitabine, or paclitaxel induces the coordinate transcriptional induction of CD47, CD73, and PDL1 mRNA and protein expression, leading to a marked increase in the percentage of CD47+CD73+PDL1+ breast cancer cells...
January 24, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29365031/unravelling-triple-negative-breast-cancer-molecular-heterogeneity-using-an-integrative-multiomic-analysis
#12
Y Bareche, D Venet, M Ignatiadis, P Aftimos, M Piccart, F Rothe, C Sotiriou
Background: Recent efforts of genome-wide gene expression profiling analyses have improved our understanding of the biological complexity and diversity of triple negative breast cancers (TNBCs) reporting, at least 6 different molecular subtypes of TNBC namely Basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL) and luminal androgen receptor (LAR). However, little is known regarding the potential driving molecular events within each subtype, their difference in survival and response to therapy...
January 22, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29363363/nivolumab-for-the-treatment-of-urothelial-cancers
#13
Min Yuen Teo, Jonathan E Rosenberg
Advanced urothelial cancer patients had limited therapeutic options following failure of platinum-based chemotherapy. The recognition that anti-PD1/PDL1 immune checkpoint inhibitors lead to dramatic and durable responses in a subset of patients has transformed the therapeutic landscape of these cancers. Since May 2016, five agents targeting this pathway have been approved by the US FDA, including the PD-1 inhibitor nivolumab. Areas covered: The purpose of this paper was to review the safety, activity and efficacy of nivolumab, an anti-PD1 checkpoint inhibitor for the treatment of locally-advanced or metastatic urothelial cancers...
January 24, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29345058/frontline-science-anti-pd-l1-protects-against-infection-with-common-bacterial-pathogens-after-burn-injury
#14
Naeem K Patil, Liming Luan, Julia K Bohannon, Antonio Hernandez, Yin Guo, Edward R Sherwood
Burn patients are susceptible to infections due, in part, to immune dysfunction. Upregulation of programmed death-1 (PD-1) receptor on T cells and programmed cell death ligand-1 (PD-L1) on myeloid cells contribute to immune dysfunction in nonburn-related sepsis. We hypothesized that PD-1/PDL1 interactions contribute to immune dysfunction after burn injury. To determine the impact of burn injury and infection on PD-L1, PD-1 and costimulatory receptor expression by leukocytes and its relationship to T cell functions...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29336717/pd1-protein-expression-in-tumor-infiltrated-lymphocytes-rather-than-pdl1-in-tumor-cells-predicts-survival-in-triple-negative-breast-cancer
#15
Xinyu Ren, Huanwen Wu, Junliang Lu, Yuhan Zhang, Yufeng Luo, Qianqian Xu, Songjie Shen, Zhiyong Liang
ABASTRACT To determine PD1/PDL1 expression status in triple-negative breast cancer (TNBC) at both protein and mRNA levels, and to analyze the relationship between their expression and clinical parameters of the TNBC patients. Immunohistochemistry and RNAscope were used to semi quantitively evaluate PD1/PDL1 protein and mRNA expression in 195 TNBC cases on tissue microarrays. Tumor infiltrating lymphocyte (TILs) abundance was assessed using hematoxylin-eosin staining.Both tumor cells and TILs expressed PDL1...
January 16, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29331888/a-longitudinal-analysis-of-ido-and-pdl1-expression-during-immune-or-targeted-therapy-in-advanced-melanoma
#16
Lukas Krähenbühl, Simone M Goldinger, Joanna Mangana, Katrin Kerl, Ines Chevolet, Liève Brochez, Christine Horak, Mitch Levesque, Reinhard Dummer, Phil F Cheng
A deepened understanding of the cellular and molecular processes in the tumor microenvironment is necessary for the development of precision immunotherapy (IT). We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry in paired biopsies from various organs of 43 metastatic melanoma patients treated with IT and targeted therapy (TT). Intraindividual biopsies taken after a period of weeks to months demonstrate discordant results in 30% of the cases. Overlap of IDO and PDL1 increased after therapy...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29322427/immunophenotyping-of-pediatric-brain-tumors-correlating-immune-infiltrate-with-histology-mutational-load-and-survival-and-assessing-clonal-t-cell-response
#17
Ashley S Plant, Shohei Koyama, Claire Sinai, Isaac H Solomon, Gabriel K Griffin, Keith L Ligon, Pratiti Bandopadhayay, Rebecca Betensky, Ryan Emerson, Glenn Dranoff, Mark W Kieran, Jerome Ritz
There is little known regarding the immune infiltrate present in pediatric brain tumors and how this compares to what is known about histologically similar adult tumors and its correlation with survival. Here, we provide a descriptive analysis of the immune infiltrate of 22 fresh pediatric brain tumor tissue samples of mixed diagnoses and 40 peripheral blood samples. Samples were analyzed using a flow cytometry panel containing markers for immune cell subtypes, costimulatory markers, inhibitory signals, and markers of activation...
January 10, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29312678/why-anti-pd1-pdl1-therapy-is-so-effective-another-piece-in-the-puzzle
#18
EDITORIAL
Antonio Marchetti, Alessia Di Lorito, Fiamma Buttitta
No abstract text is available yet for this article.
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29307625/prognostic-role-of-tumoral-pdl1-expression-and-peritumoral-foxp3-lymphocytes-in-vulvar-melanomas
#19
Agata Chłopik, M Angelica Selim, Yan Peng, Cheng-Lin Wu, Gemma Tell-Marti, Kristen M Paral, Sara C Shalin, Stefan Kraft, Chao-Kai Hsu, Christopher R Shea, Susana Puig, Maria-Teresa Fernandez-Figueras, Wojciech Biernat, Janusz Ryś, Andrzej Marszalek, Mai P Hoang
Prognostic role of PDL1 expression, CD8+ and FoxP3+ lymphocytes in vulvar melanomas has not been studied. We correlated PDL1 expression, and CD8+ and FoxP3+ immune infiltrates with clinicopathologic variables and patient outcomes in a series of 75 vulvar melanomas. Tumoral PDL1 expression (>5%) was seen in 23% of cases. By Fisher's Exact test, PDL1 expression and peritumoral FoxP3+ lymphocytes significantly correlated with less disease-specific death. By linear regression analysis, correlations between tumoral PDL1 expression with the density of tumoral CD8+ and peritumoral CD8+ lymphocytes; tumoral FoxP3+ with tumoral CD8+ lymphocytes; and peritumoral FoxP3+ with peritumoral CD8+ lymphocytes were observed...
January 4, 2018: Human Pathology
https://www.readbyqxmd.com/read/29306075/fasn-tgf-%C3%AE-1-pd-l1-axis-contributes-to-the-development-of-resistance-to-nk-cell-cytotoxicity-of-cisplatin-resistant-lung-cancer-cells
#20
MingJing Shen, Ying Tsai, Rongying Zhu, Peter C Keng, Yongbing Chen, Yuhchyau Chen, Soo Ok Lee
Cisplatin remains the most effective therapy for non-small cell lung cancer (NSCLC). We previously have found cisplatin-resistant lung cancer cells (A549CisR and H157CisR) were more resistant to natural killer (NK) cell-mediated cytotoxicity than parental cells. We also discovered that fatty acid synthase (FASN) levels in cisplatin-resistant cells were significantly higher than parental cells. To reveal whether a link exists between the up-regulated FASN levels and higher resistance to NK cell cytotoxicity, we performed inhibition studies using a FASN inhibitor and applied the FASN knockdown approach...
January 3, 2018: Biochimica et Biophysica Acta
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