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https://www.readbyqxmd.com/read/29016555/interleukin-10-regulated-tumour-tolerance-in-non-small-cell-lung-cancer
#1
Julius Malte Vahl, Juliane Friedrich, Susanne Mittler, Sonja Trump, Lisanne Heim, Katerina Kachler, Liubov Balabko, Nicole Fuhrich, Carol-Immanuel Geppert, Denis Iulian Trufa, Nina Sopel, Ralf Rieker, Horia Sirbu, Susetta Finotto
BACKGROUND: Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape. METHODS: Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer. RESULTS: Here we discovered a positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the lung with tumour diameter in patients with lung cancer (non-small cell lung cancer), the most life-threatening cancer type worldwide...
October 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28974431/adenovirotherapy-delivering-cytokine-and-checkpoint-inhibitor-augments-car-t-cells-against-metastatic-head-and-neck-cancer
#2
Amanda Rosewell Shaw, Caroline E Porter, Norihiro Watanabe, Kiyonori Tanoue, Andrew Sikora, Stephen Gottschalk, Malcolm K Brenner, Masataka Suzuki
In solid tumors, chimeric antigen receptor (CAR)-modified T cells must overcome the challenges of the immunosuppressive tumor microenvironment. We hypothesized that pre-treating tumors with our binary oncolytic adenovirus (CAd), which produces local oncolysis and expresses immunostimulatory molecules, would enhance the antitumor activity of HER2-specific CAR T cells, which alone are insufficient to cure solid tumors. We tested multiple cytokines in conjunction with PD-L1-blocking antibody and found that Ad-derived IL-12p70 prevents the loss of HER2...
September 14, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28968536/tumor-vasculature-normalization-by-orally-fed-erlotinib-to-modulate-the-tumor-microenvironment-for-enhanced-cancer-nanomedicine-and-immunotherapy
#3
Qian Chen, Ligeng Xu, Jiawen Chen, Zhijuan Yang, Chao Liang, Yu Yang, Zhuang Liu
The abnormal tumor vasculature is one of key reasons that lead to the limited tumor perfusion as well as hypoxic and immunosuppressive tumor microenvironment (TME). Herein, we uncover that by normalizing the tumor vasculature with erlotinib, a specific inhibitor of epidermal growth factor receptor (EGFR), the tumor perfusion and tumor oxygenation statuses in different types of tumors including murine breast tumors, colorectal tumors, and squamous cell carcinoma tumors, could be remarkably enhanced. As the results, the tumor uptake of drug-loaded nanoparticles as well as their interstitial penetration within the tumor would be greatly increased for mice pre-treated with erlotinib at the oral feeding dose of 50 mg/kg, leading to remarkably improved chemotherapeutic efficacy of nanomedicine...
December 2017: Biomaterials
https://www.readbyqxmd.com/read/28938530/cd3xpdl1-bi-specific-t-cell-engager-bite-simultaneously-activates-t-cells-and-nkt-cells-kills-pdl1-tumor-cells-and-extends-the-survival-of-tumor-bearing-humanized-mice
#4
Lucas A Horn, Nicholas G Ciavattone, Ryan Atkinson, Netsanet Woldergerima, Julia Wolf, Virginia K Clements, Pratima Sinha, Munanchu Poudel, Suzanne Ostrand-Rosenberg
Bi-specific T cell engagers (BiTEs) activate T cells through CD3 and target activated T cells to tumor-expressed antigens. BiTEs have shown therapeutic efficacy in patients with liquid tumors; however, they do not benefit all patients. Anti-tumor immunity is limited by Programmed Death 1 (PD1) pathway-mediated immune suppression, and patients who do not benefit from existing BiTES may be non-responders because their T cells are anergized via the PD1 pathway. We have designed a BiTE that activates and targets both T cells and NKT cells to PDL1(+) cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28932645/intratumor-heterogeneity-of-immune-checkpoints-in-primary-renal-cell-cancer-focus-on-hla-g-ilt2-ilt4
#5
Nathalie Rouas-Freiss, Joel LeMaoult, Jérôme Verine, Diana Tronik-Le Roux, Stéphane Culine, Christophe Hennequin, François Desgrandchamps, Edgardo D Carosella
The establishment and maintenance of anti-tumor immune responses are the objectives of cancer immunotherapy. Despite recent promising advances, the effectiveness of these approaches has been limited by the multiple immunosuppressive mechanisms developed by tumors (checkpoint). The aim of the present study was to demonstrate intratumor heterogeneity at the levels of immune escape strategies and tumor-host relationships. We focused on well-known checkpoints such as PD1/PDL1 and on a new checkpoint involving HLA-G and its receptors ILT2/ILT4...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931635/a-computational-multiscale-agent-based-model-for-simulating-spatio-temporal-tumour-immune-response-to-pd1-and-pdl1-inhibition
#6
Chang Gong, Oleg Milberg, Bing Wang, Paolo Vicini, Rajesh Narwal, Lorin Roskos, Aleksander S Popel
When the immune system responds to tumour development, patterns of immune infiltrates emerge, highlighted by the expression of immune checkpoint-related molecules such as PDL1 on the surface of cancer cells. Such spatial heterogeneity carries information on intrinsic characteristics of the tumour lesion for individual patients, and thus is a potential source for biomarkers for anti-tumour therapeutics. We developed a systems biology multiscale agent-based model to capture the interactions between immune cells and cancer cells, and analysed the emergent global behaviour during tumour development and immunotherapy...
September 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28915924/pdl1-and-ldha-act-as-cernas-in-triple-negative-breast-cancer-by-regulating-mir-34a
#7
Xiaojia Huang, Xinhua Xie, Hua Wang, Xiangsheng Xiao, Lu Yang, Zhi Tian, Xiaofang Guo, Lijuan Zhang, Hailin Tang, Xiaoming Xie
BACKGROUD: The purpose of this study was to elucidate the regulation of programmed death ligand 1 (PDL1), lactate dehydrogenase A (LDHA) and miR-34a in triple negative breast cancer (TNBC) and to explore the function and mechanism of PDL1 and LDHA as competitive endogenous RNAs (ceRNAs) in TNBC via regulation of miR-34a. METHODS: Western blotting, quantitative RT-PCR (qRT-PCR) and immunohistochemistry (IHC) assays were conducted to explore the expression of PDL1, LDHA and miR-34a in TNBC and correlations between them...
September 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28912094/selection-of-pd1-pd-l1-x-aptamers
#8
Hongyu Wang, Curtis H Lam, Xin Li, Derek L West, Xianbin Yang
Specific, chemically modified aptamers (X-Aptamers) were identified against two immune checkpoint proteins, recombinant Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1). Selections were performed using a bead-based X-Aptamer (XA) library containing several different amino acid functional groups attached to dU at the 5-position. The binding affinities and specificities of the selected XA-PD1 and XA-PDL1 were validated by hPD-1 and hPD-L1 expression cells, as well as by binding to human pancreatic ductal adenocarcinoma tissue...
September 11, 2017: Biochimie
https://www.readbyqxmd.com/read/28892130/fgl2-deteriorates-cardiac-function-in-experimental-autoimmune-myocarditis-rats-through-regulation-of-pd-1-and-inflammatory-cytokines
#9
Zhenzhong Zheng, Yinghui Yu, Ratnakar Potla, Yujing Wu, Hao Wu
PD-1 plays an important role in protecting against inflammation and myocyte damage in T cell mediated myocarditis. To understand whether FGL2 can affect the role of PD-1/PD-L1 pathway in experimental autoimmune myocarditis (EAM),we investigated the cardiac function in EAM rats overexpressing FGL2. Overexpression of FGL2 significantly decreased PD-1 and deteriorated cardiac function in autoimmune myocarditis rats. Histopathology revealed increased inflammatory cell infiltrate in EAM-FGL2 rats compared to the control groups (EAM, EAM-GFP, and NC)...
September 11, 2017: Immunology
https://www.readbyqxmd.com/read/28886030/analysis-of-the-whole-transcriptome-from-gingivo-buccal-squamous-cell-carcinoma-reveals-deregulated-immune-landscape-and-suggests-targets-for-immunotherapy
#10
Richa Singh, Navonil De Sarkar, Sumanta Sarkar, Roshni Roy, Esita Chattopadhyay, Anindita Ray, Nidhan K Biswas, Arindam Maitra, Bidyut Roy
BACKGROUND: Gingivo-buccal squamous cell carcinoma (GBSCC) is one of the most common oral cavity cancers in India with less than 50% patients surviving past 5 years. Here, we report a whole transcriptome profile on a batch of GBSCC tumours with diverse tobacco usage habits. The study provides an entire landscape of altered expression with an emphasis on searching for targets with therapeutic potential. METHODS: Whole transcriptomes of 12 GBSCC tumours and adjacent normal tissues were sequenced and analysed to explore differential expression of genes...
2017: PloS One
https://www.readbyqxmd.com/read/28878768/natural-igm-and-tlr-agonists-switch-murine-splenic-pan-b-to-regulatory-cells-that-suppress-ischemia-induced-innate-inflammation-via-regulating-nkt-1-cells
#11
Peter I Lobo, Kailo H Schlegel, Amandeep Bajwa, Liping Huang, Mark D Okusa
Natural IgM anti-leukocyte autoantibodies (IgM-ALAs) inhibit inflammation by several mechanisms. Here, we show that pan-B cells and bone marrow-derived dendritic cells (BMDCs) are switched to regulatory cells when pretreated ex vivo with IgM. B cells are also switched to regulatory cells when pretreated ex vivo with CpG but not with LPS. Pre-emptive infusion of such ex vivo induced regulatory cells protects C57BL/6 mice from ischemia-induced acute kidney injury (AKI) via regulation of in vivo NKT-1 cells, which normally amplify the innate inflammatory response to DAMPS released after reperfusion of the ischemic kidney...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28871357/-immunotherapy-as-modern-tumor-treatment
#12
REVIEW
C Grüllich
BACKGROUND: The specific immune system is capable of preventing the development of tumor diseases and stimulation of cytotoxic T‑lymphocytes can repress existing tumors. The activation of T‑lymphocytes is influenced by a new class of antibody-based medication, the immune checkpoint inhibitors. METHODS: Review of the scientific background and the published clinical trials on the activity and approval of immune checkpoint inhibitors for various tumor diseases...
September 4, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28834746/pdl1-signals-through-conserved-sequence-motifs-to-overcome-interferon-mediated-cytotoxicity
#13
Maria Gato-Cañas, Miren Zuazo, Hugo Arasanz, Maria Ibañez-Vea, Laura Lorenzo, Gonzalo Fernandez-Hinojal, Ruth Vera, Cristian Smerdou, Eva Martisova, Imanol Arozarena, Claudia Wellbrock, Diana Llopiz, Marta Ruiz, Pablo Sarobe, Karine Breckpot, Grazyna Kochan, David Escors
PDL1 blockade produces remarkable clinical responses, thought to occur by T cell reactivation through prevention of PDL1-PD1 T cell inhibitory interactions. Here, we find that PDL1 cell-intrinsic signaling protects cancer cells from interferon (IFN) cytotoxicity and accelerates tumor progression. PDL1 inhibited IFN signal transduction through a conserved class of sequence motifs that mediate crosstalk with IFN signaling. Abrogation of PDL1 expression or antibody-mediated PDL1 blockade strongly sensitized cancer cells to IFN cytotoxicity through a STAT3/caspase-7-dependent pathway...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28832074/programmed-death-ligand-1-pd-l1-expression-in-malignant-mesenchymal-tumors
#14
Kemal Kösemehmetoğlu, Ece Özoğul, Berrin Babaoğlu, Gaye Güler Tezel, Gökhan Gedikoğlu
OBJECTIVE: Programmed death ligand 1 (PD-L1) found on tumor cells has recently been reported to have a key role in the development and dissemination of many tumors, such as lung and breast carcinomas. In this study, we retrospectively analyzed PD-L1 expression among different types of sarcomas. MATERIAL AND METHOD: Tissue microarrays of 3-4 mm diameter were composed from paraffin blocks of 222 various sarcomas. Slides prepared from microarrays were stained for PD-L1 antibody (Cell Signaling, E1L3N®) using Leica Bond Autostainer...
2017: Türk Patoloji Dergisi
https://www.readbyqxmd.com/read/28819064/the-tumor-microenvironment-regulates-sensitivity-of-murine-lung-tumors-to-pd-1-pd-l1-antibody-blockade
#15
Howard Y Li, Maria McSharry, Bonnie Bullock, Teresa T Nguyen, Jeff Kwak, Joanna M Poczobutt, Trisha R Sippel, Lynn E Heasley, Mary C Weiser-Evans, Eric T Clambey, Raphael A Nemenoff
Immune checkpoint inhibitors targeting the interaction between programmed cell death-1 (PD-1) and its ligand PD-L1 induce tumor regression in a subset of non-small cell lung cancer patients. However, clinical response rates are less than 25%. Evaluation of combinations of immunotherapy with existing therapies requires appropriate preclinical animal models. In this study, murine lung cancer cells (CMT167 and LLC) were implanted either orthotopically in the lung or subcutaneously in syngeneic mice, and response to anti-PD-1/PD-L1 therapy was determined...
September 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28795418/cd274-pdl1-and-jak2-genomic-amplifications-in-pulmonary-squamous-cell-and-adenocarcinoma-patients
#16
Sergi Clavé, Lara Pijuan, David Casadevall, Álvaro Taus, Javier Gimeno, Sílvia Hernández-Llodrà, María Rodríguez-Rivera, Marta Lorenzo, Sílvia Menéndez, Joan Albanell, Blanca Espinet, Edurne Arriola, Marta Salido
AIMS: CD274 (PDL1) and JAK2 (9p24.1) gene amplifications have been recently described in pulmonary carcinomas in association with PD-L1 protein expression. Also, PTEN loss have been explored preclinically in relation with PD-L1 expression. It remains to be determined if these genomic alterations may affect PD-L1 expression levels in non-small cell lung cancer. METHODS AND RESULTS: PD-L1 and PTEN protein expression by IHC, and CD274, JAK2 and PTEN gene copy number alterations (CNAs) by FISH were studied in 171 pulmonary carcinoma specimens...
August 10, 2017: Histopathology
https://www.readbyqxmd.com/read/28782050/theranostic-gold-nanoantennas-for-simultaneous-multiplexed-raman-imaging-of-immunomarkers-and-photothermal-therapy
#17
Joseph A Webb, Yu-Chuan Ou, Shannon Faley, Eden P Paul, Joseph P Hittinger, Camden C Cutright, Eugene C Lin, Leon M Bellan, Rizia Bardhan
In this study, we demonstrate the theranostic capability of actively targeted, site-specific multibranched gold nanoantennas (MGNs) in triple-negative breast cancer (TNBC) cells in vitro. By utilizing multiplexed surface-enhanced Raman scattering (SERS) imaging, enabled by the narrow peak widths of Raman signatures, we simultaneously targeted immune checkpoint receptor programmed death ligand 1 (PDL1) and the epidermal growth factor receptor (EGFR) overexpressed in TNBC cells. A 1:1 mixture of MGNs functionalized with anti-PDL1 antibodies and Raman tag 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB) and MGNs functionalized with anti-EGFR antibodies and Raman tag para-mercaptobenzoic acid (pMBA) were incubated with the cells...
July 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28754220/-metastatic-melanoma-in-placenta-a-new-case-with-pdl1-immunostaining
#18
Brice Poreau, Hervé Sartelet
No abstract text is available yet for this article.
July 25, 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28739716/clinical-significance-of-pd1-and-pdl1-in-human-breast-cancer
#19
Michal Uhercik, Andrew J Sanders, Sioned Owen, Eleri L Davies, Anup K Sharma, Wen G Jiang, Kefah Mokbel
BACKGROUND/AIM: Programmed death 1 (PD1) and its ligand programmed death ligand 1 (PDL1) form a pathway which when activated is thought to result in suppression of antitumor adaptive responses, influencing antitumor immunity. With potential targeted therapies emerging against PDL1, we investigated the clinical significance of mRNA expression levels of PD1 and PDL1 in our breast cancer cohort to explore its association with disease progression and prognosis. Previous studies evaluating the expression of PD1 and PDL1 (mRNA or protein) and its association with prognosis in breast cancer showed both positive and negative correlations and hence remain controversial...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28728868/pdl1-expression-in-desmoplastic-melanoma-is-associated-with-tumor-aggressiveness-and-progression
#20
Stefan Kraft, Maria-Teresa Fernandez-Figueras, Nina A Richarz, Keith T Flaherty, Mai P Hoang
BACKGROUND: The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear. METHODS: We correlated PDL1, p53, and Ki-67 expression with CD8(+) and FoxP3(+) immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas. RESULTS: Tumoral PDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis...
September 2017: Journal of the American Academy of Dermatology
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