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pd-l1 and EGFR

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https://www.readbyqxmd.com/read/28319808/identifying-regulatory-posttranslational-modifications-of-pd-l1-a-focus-on-monoubiquitinaton
#1
Henrick Horita, Andy Law, Soonjin Hong, Kim Middleton
A set of high-affinity, high-specificity posttranslational modification (PTM) enrichment tools was developed to generate an unbiased snapshot of four key PTM profiles (tyrosine phosphorylation, acetylation, ubiquitination, and SUMOylation 2/3) for the clinically important protein programmed cell death ligand 1 (PD-L1). The results showed that epidermal growth factor (EGF) treatment induced tyrosine phosphorylation, acetylation, and ubiquitination of PD-L1. Further characterization of EGF-induced PD-L1 ubiquitination revealed a significant increase in mono- and multiubiquitination of PD-L1 that occurred on glycosylated PD-L1...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28301925/retrospective-molecular-epidemiology-study-of-pd-l1-expression-in-patients-with-egfr-mutant-non-small-cell-lung-cancer
#2
Jong Ho Cho, Wei Zhou, Yoon-La Choi, Jong-Mu Sun, Hyejoo Choi, Tae-Eun Kim, Marisa Dolled-Filhart, Kenneth Emancipator, Mary Anne Rutkowski, Jhingook Kim
Purpose: Data are limited on PD-L1 expression in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Materials and Methods: We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free (RFS) and overall survival in 319 patients with EGFR-mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS)...
March 17, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28297818/-research-progress-of-pd-1-pd-l1-pathway-in-non-small-cell-lung-cancer-with-egfr
#3
A Y Zhong, Y She, M H Shi
No abstract text is available yet for this article.
March 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28260924/impact-of-gefitinib-in-early-stage-treatment-on-circulating-cytokines-and-lymphocytes-for-patients-with-advanced-non-small-cell-lung-cancer
#4
Jin Sheng, Wenfeng Fang, Xia Liu, Shan Xing, Jianhua Zhan, Yuxiang Ma, Yan Huang, Ningning Zhou, Hongyun Zhao, Li Zhang
OBJECTIVES: The impact of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) on the human immune system remains undefined. This study illustrates the immunomodulatory effect of gefitinib in patients with advanced non-small cell lung cancer (NSCLC) and its relevant prognostic significance. PATIENTS AND METHODS: Peripheral blood samples were collected from 54 patients at baseline and after 4 weeks of gefitinib treatment. Circulating lymphocyte populations and cytokine levels were measured...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28259530/association-between-pd-l1-expression-and-driven-gene-status-in-nsclc-a-meta-analysis
#5
D Li, X Zhu, H Wang, N Li
PURPOSE: We explored the potential clinical association between programmed death-ligand 1 (PD-L1) expression and driven gene status in non-small cell lung cancer (NSCLC). METHODS: We systemically searched through October 2015. Odd ratios (ORs) with 95% CIs were calculated to examine the association of PD-L1 expression with driven gene status. A random- or fixed-effects model was used. RESULTS: Nine studies were identified. KRAS-mutant tumors were more likely to be PD-L1 positive than KRAS-wild type tumors (51% vs 36%; OR 1...
February 21, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28243112/induction-of-pd-l1-expression-by-epidermal-growth-factor-receptor-mediated-signaling-in-esophageal-squamous-cell-carcinoma
#6
Wencheng Zhang, Qingsong Pang, Cihui Yan, Qifeng Wang, Jingsong Yang, Shufei Yu, Xiao Liu, Zhiyong Yuan, Ping Wang, Zefen Xiao
PURPOSE: The purpose of this study was to investigate the potential effect of activation of epidermal growth factor receptor (EGFR) signaling pathway on the expression of programmed death-ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) cells with EGFR overexpression. METHODS: Flow cytometry and Western blot methods were used to assess PD-L1 expression on ESCC cells when EGFR signaling pathway was activated by epidermal growth factor (EGF) with or without EGFR-specific inhibitor AG-1478, and then EGFR signaling array was applied to analyze the potential signaling pathways involved...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28236980/significance-of-immune-checkpoint-proteins-in-egfr-mutant-non-small-cell-lung-cancer
#7
Ross A Soo, Hye Ryun Kim, Bernadette Reyna Asuncion, Zul Fazreen, Mohamed Feroz Mohd Omar, Maria Cynthia Herrera, Joey Sze Yun Lim, Grace Sia, Richie Soong, Byoung-Chul Cho
OBJECTIVES: To characterize the expression of PD-L1, PD-1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and T-cell immunoglobulin and mucin-domain containing-3 (TIM3) in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Samples from 90 patients with newly diagnosed advanced stage NSCLC harboring EGFR mutations and treated with first line EGFR tyrosine kinase inhibitors (TKI) within 3 months of diagnosis were stained for CTLA-4, PD-L1, PD-1, TIM-3 and CD3 expression by immunohistochemistry...
March 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#8
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28212996/analysis-of-a-panel-of-druggable-gene-mutations-and-of-alk-and-pd-l1-expression-in-a-series-of-thymic-epithelial-tumors-tets
#9
Marcello Tiseo, Angela Damato, Lucia Longo, Fausto Barbieri, Federica Bertolini, Alessandro Stefani, Mario Migaldi, Letizia Gnetti, Roberta Camisa, Paola Bordi, Sebastiano Buti, Giulio Rossi
INTRODUCTION: Thymic epithelial tumors (TETs) are rare neoplasms with different prognosis lacking consistent molecular alterations possibly leading to targeted therapy. We collected a consecutive series of TETs aimed at investigating the mutational status of druggable genes (EGFR, c-KIT, KRAS, BRAF, PDGFR-alpha and -beta, HER2 and c-MET) and the expression of ALK and PD-L1. PATIENTS AND METHODS: One hundred twelve consecutive cases of TETs and relative clinico-pathologic features were collected...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28193529/heterogeneity-in-immune-marker-expression-after-acquisition-of-resistance-to-egfr-kinase-inhibitors-analysis-of-a-case-with-small-cell-lung-cancer-transformation
#10
Kenichi Suda, Isao Murakami, Hui Yu, Jihye Kim, Kim Ellison, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
INTRODUCTION: Expression of immune-markers is of scientific interest due to their potential roles as predictive biomarkers for immunotherapy. Although the microenvironment of metastatic tumors and/or therapy-inducible histological transformation may affect the expression of these immune-markers, there is little data regarding this context. METHODS: A 76-year-old never-smoking female with epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma (AC) acquired resistance to gefitinib...
February 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28192623/pd-l1-is-prognostic-factor-in-esophageal-squamous-cell-carcinoma-and-is-associated-with-egfr
#11
Wencheng Zhang, Qingsong Pang, Xiaodong Zhang, Cihui Yan, Qifeng Wang, Jinsong Yang, Shufei Yu, Xiao Liu, Yi Pan, Zhiyong Yuan, Ping Wang, Zefen Xiao
Programmed death-ligand 1 (PD-L1) expression either indicates immune inhibitory status or concurrent immune response. Although the relationship between PD-L1 and clinical outcomes has been studied widely in recent years, its role in prognosis of esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we assessed the significance of PD-L1 in ESCC and its association with epidermal growth factor receptor (EGFR) and radiation response. We found that PD-L1 was present both on the surface of tumor cells and tumor-infiltrating immune cells...
February 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28187748/characterization-of-ovarian-clear-cell-carcinoma-using-target-drug-based-molecular-biomarkers-implications-for-personalized-cancer-therapy
#12
Mengjiao Li, Haoran Li, Fei Liu, Rui Bi, Xiaoyu Tu, Lihua Chen, Shuang Ye, Xi Cheng
BACKGROUND: It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC)...
February 10, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28183254/metastatic-colorectal-cancer-role-of-target-therapies-and-future-perspectives
#13
Anna Nappi, Massimiliano Berretta, Carmela Romano, Salvatore Tafuto, Antonino Cassata, Rossana Casaretti, Lucrezia Silvestro, Chiara De Divitiis, Lara Alessandrini, Francesco Fiorica, Alessandro Ottaiano, Guglielmo Nasti
Today, we are experiencing a real cultural revolution in the therapeutic approach to cancer of the colon - rectum, that, by orphan disease, it is now becoming an important paradigm of scientific innovations and concepts. Survival of patients with metastatic colorectal cancer (m-CRC) has been significantly improved with the introduction of the monoclonal antibodies that have as target the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). Novel agents such as aflibercept and regorafenib have recently been approved...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28152786/first-line-treatment-of-metastatic-nsclc-mnsclc-patients-without-actionable-mutations-in-u-s-community-oncology-clinical-practice
#14
Ashwini Arunachalam, Thomas A Burke, Xiting Cao, Amy P Abernethy, David Paul Carbone
307 Background: Benchmarking high quality care requires defining optimally effective practice patterns. As first step, contemporary real-world practice must be detailed. The purpose of this study is to describe patient flow from diagnosis of mNSCLC to initiation of anti-cancer drug therapy in patients without known EGFR/ALK genomic tumor aberrations; the characteristics and first-line (1L) anti-cancer treatment of these patients, including induction and maintenance therapy. METHODS: Retrospective database cohort study using data from an oncology EHR system, representing 17% of incident cancer cases from US community setting...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28137741/pd-l1-protein-expression-assessed-by-immunohistochemistry-is-neither-prognostic-nor-predictive-of-benefit-from-adjuvant-chemotherapy-in-resected-non-small-cell-lung-cancer
#15
M-S Tsao, G Le Teuff, F A Shepherd, C Landais, P Hainaut, M Filipits, R Pirker, T Le Chevalier, S Graziano, R Kratze, J-C Soria, J-P Pignon, L Seymour, E Brambilla
BACKGROUND: The expression of programmed death (PD) ligand 1 (PD-L1) protein expression assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 immune checkpoint inhibitor therapies in advanced non-small cell lung carcinoma (NSCLC). The efficacy of several agents appears correlated with PD-L1 expression. It remains controversial whether PD-L1 is prognostic in NSCLC. We assessed the prognostic value of PD-L1 IHC and its predictive role for adjuvant chemotherapy in early stage NSCLC...
January 30, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28132868/lag-3-protein-expression-in-non-small-cell-lung-cancer-and-its-relationship-with-pd-1-pd-l1-and-tumor-infiltrating-lymphocytes
#16
Yayi He, Hui Yu, Leslie Rozeboom, Christopher J Rivard, Kim Ellison, Rafal Dziadziuszko, Kenichi Suda, Shengxiang Ren, Chunyan Wu, Likun Hou, Caicun Zhou, Fred R Hirsch
BACKGROUND: Immunotherapy targeting the programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1) checkpoint has shown promising efficacy in patients with non-small cell lung cancer (NSCLC). Lymphocyte activation gene-3 (LAG-3) is another important checkpoint, and its role in NSCLC is still not clear. In this study, we investigated LAG-3 protein expression and its correlation with PD-1, PD-L1, tumor-infiltrating lymphocytes (TILs), and association with survival in NSCLC. METHODS: The expression of LAG-3 (EPR4392, Abcam) protein was assessed in 55 NSCLC cell lines by immunohistochemistry (IHC)...
January 26, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28104537/correlation-between-classic-driver-oncogene-mutations-in-egfr-alk-or-ros1-and-22c3-pd-l1-%C3%A2-50-expression-in-lung-adenocarcinoma
#17
Deepa Rangachari, Paul A VanderLaan, Meghan Shea, Xiuning Le, Mark S Huberman, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: Targeted somatic genomic analysis (EGFR, anaplastic lymphoma receptor tyrosine kinase gene [ALK], and ROS1) and programmed death ligand 1 (PD-L1) tumor proportion score (TPS) determined by immunohistochemistry (IHC) are used for selection of first-line therapies in advanced lung cancer; however, the frequency of overlap of these biomarkers in routine clinical practice is poorly reported. METHODS: We retrospectively probed the first 71 pairs of patients with lung adenocarcinoma from our institution...
January 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28096505/the-neuropilin-2-isoform-nrp2b-uniquely-supports-tgf%C3%AE-mediated-progression-in-lung-cancer
#18
Robert M Gemmill, Patrick Nasarre, Joyce Nair-Menon, Federico Cappuzzo, Lorenza Landi, Armida D'Incecco, Hidetaka Uramoto, Takeshi Yoshida, Eric B Haura, Kent Armeson, Harry A Drabkin
Neuropilins (NRP1 and NRP2) are co-receptors for heparin-binding growth factors and class 3 semaphorins. Different isoforms of NRP1 and NRP2 are produced by alternative splicing. We found that in non-small cell lung cancer (NSCLC) cell lines, transforming growth factor-β (TGFβ) signaling preferentially increased the abundance of NRP2b. NRP2b and NRP2a differ only in their carboxyl-terminal regions. Although the presence of NRP2b inhibited cultured cell proliferation and primary tumor growth, NRP2b enhanced cellular migration, invasion into Matrigel, and tumorsphere formation in cultured cells in response to TGFβ signaling and promoted metastasis in xenograft mouse models...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28057155/-level-of-soluble-programmed-death-1-ligand-1-in-peripheral-blood-of-patients-with-advanced-epidermal-growth-factor-receptor-mutated-lung-adenocarcinoma-and-its-clinical-implications
#19
L Q Zhang, Y Chen, X Pan, Y F Xing, M H Shi, Y J Chen
Objective: To analyze the expression of soluble programmed death ligand 1 (sPD-L1) in the serum of patients with advanced epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma and to explore its clinical implications. Methods: Seventy-two patients with EGFR mutated advanced lung adenocarcinoma (EGFR mutation group) were included from the Department of Respiratory Diseases in The Second Affiliated Hospital of Soochow University from May 2015 to July 2016. Thirty-one patients with advanced EGFR wild type (WT) lung adenocarcinoma [EGFR WT group, diagnosed via mini specimens from bronchoscopy or transthoracic needle aspiration biopsy (TNAB), matching in sex, age and tumor stage with EGFR mutation group] were also enrolled as controls...
December 27, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28056301/-expression-of-pd-1-pd-l1-in-lung-adenocarcinoma-and-correlation-with-epidermal-growth-factor-receptor-mutation-status
#20
Y Wang, J P Da, X H Wang, A P Song, H Chen, H L Zhang, S Chen, D W Wang
Objective: To investigate the expression of programmed cell death-1(PD-1) and programmed cell death-ligand 1(PD-L1) in lung adenocarcinoma in correlation with clinical pathological parameters, especially with regard to different epidermal growth factor receptor (EGFR) mutation status. Methods: One hundred and nine cases of lung adenocarcinoma were collected during the period from Aug. 2010 to Jan. 2016, including 51 cases of EGFR wild type and 58 cases of EGFR mutations. Immunohistochemistry was used to detect PD-1/PD-L1 protein expression...
December 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
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