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pd-l1, lung cancer

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https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#1
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28925087/relationship-of-tumor-pd-l1-cd274-expression-with-lower-mortality-in-lung-high-grade-neuroendocrine-tumor
#2
Kentaro Inamura, Yusuke Yokouchi, Maki Kobayashi, Hironori Ninomiya, Rie Sakakibara, Makoto Nishio, Sakae Okumura, Yuichi Ishikawa
Programmed death-ligand 1 (PD-L1) promotes immunosuppression by binding to PD-1 on T lymphocytes. Although tumor PD-L1 expression is a potential predictive marker of clinical response to anti-PD-1/PD-L1 therapy, little is known about its association with clinicopathological features, including prognosis, in high-grade neuroendocrine tumors (HGNETs), including small-cell lung carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC), of the lung. We immunohistochemically examined the membranous of expression of PD-L1 in 115 consecutive surgical cases of lung HGNET (74 SCLC cases and 41 LCNEC cases)...
September 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28923211/nivolumab-and-pembrolizumab-monoclonal-antibodies-against-programmed-cell-death-1-pd-1-that-are-interchangeable
#3
REVIEW
Vinay Prasad, Victoria Kaestner
Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1), whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance. These drugs have earned a series of FDA approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin lymphoma, and renal cell cancer...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28923100/checkpoint-inhibitor-is-active-against-large-cell-neuroendocrine-carcinoma-with-high-tumor-mutation-burden
#4
Victoria E Wang, Anatoly Urisman, Lee Albacker, Siraj Ali, Vincent Miller, Rahul Aggarwal, David Jablons
BACKGROUND: Large cell neuroendocrine tumor (LCNEC) of the lung is a rare and aggressive tumor similar to small cell lung cancer (SCLC). Thus, it is often treated similarly to SCLC in the front-line setting with a platinum doublet. However, treatment for patients beyond the first line remains undefined. CASE PRESENTATION: We report the case of a patient with stage IB LCNEC (PD-L1 negative but positive for PD-L1 amplification and tumor mutation burden high) who progressed after adjuvant chemotherapy after surgery and subsequent therapy with an antibody drug conjugate targeting a neuroendocrine-specific cell surface marker but achieved a significant and durable response with pembrolizumab, a humanized IgG4 monoclonal anti-PD-1 antibody...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28915714/the-efficacy-of-anti-pd-1-pd-l1-therapy-and-its-comparison-with-egfr-tkis-for-advanced-non-small-cell-lung-cancer
#5
REVIEW
Zhixin Sheng, Xu Zhu, Yanhua Sun, Yanxia Zhang
PURPOSE: To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC). METHODS: The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in previously treated patients with advanced NSCLC. RESULTS: Finally, we identified 14 prospective published reports including four trials of atezolizumab covering 542 subjects, three trials of pembrolizumab covering 1566 subjects, seven trials of nivolumab covering 1678 subjects...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912897/genomic-analysis-of-tumor-microenvironment-immune-types-across-14-solid-cancer-types-immunotherapeutic-implications
#6
Yu-Pei Chen, Yu Zhang, Jia-Wei Lv, Ying-Qin Li, Ya-Qin Wang, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Yan-Ping Mao, Jing-Ping Yun, Na Liu, Jun Ma
We performed a comprehensive immuno-genomic analysis of tumor microenvironment immune types (TMITs), which is classified into four groups based on PD-L1+CD8A or PD-L1+cytolytic activity (CYT) expression, across a broad spectrum of solid tumors in order to help identify patients who will benefit from anti- PD-1/PD-L1 therapy. The mRNA sequencing data from The Cancer Genome Atlas (TCGA) of 14 solid cancer types representing 6,685 tumor samples was analyzed. TMIT was classified only for those tumor types that both PD-L1 and CD8A/CYT could prefict mutation and/or neoantigen number...
2017: Theranostics
https://www.readbyqxmd.com/read/28912396/-immune-checkpoint-inhibitors-for-lung-cancer-with-egfr-mutation
#7
Hidetoshi Hayashi, Tetsuya Mitsudomi
Recent clinical evidence that anti-PD-1/PD-L1 antibody therapy is superior to cytotoxic chemotherapy for patients with non-small cell lung cancer(NSCLC)that expresses PD-L1 has lead to a paradigm shift in treatment strategies for those patients. However, efficacy of anti-PD-1/PD-L1 antibodies for patients with NSCLC harboring EGFR mutation is generally poor. This lack ofresponse is at least partially attributed to suppression oftumor infiltrating lymphocytes caused by EGFR pathway activation or to low non-synonymous mutation load in NSCLC with EGFR mutation...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28912137/enhanced-cancer-immunotherapy-by-chimeric-antigen-receptor-modified-t-cells-engineered-to-secrete-checkpoint-inhibitors
#8
Pin Wang, Si Li, Natnaree Siriwon, Xiaoyang Zhang, Shuai Yang, Tao Jin, Feng He, Yu Jeong Kim, John Mac, Zhengfei Lu, Sijie Wang, Xiaolu Han
PURPOSE: Despite favorable responses of CAR-engineered T cell therapy in patients with hematologic malignancies, the outcome has been far from satisfactory in the treatment of solid tumors, partially owing to the development of an immunosuppressive tumor microenvironment. To overcome this limitation, we engineered CAR-T cells secreting checkpoint inhibitors (CPIs) targeting PD-1 (CAR.αPD1-T) and evaluated their efficacy in a human lung carcinoma xenograft mouse model. EXPERIMENTAL DESIGN: To evaluate the effector function and expansion capacity of CAR...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28903317/pd-l1-and-c-met-expression-and-survival-in-patients-with-small-cell-lung-cancer
#9
Lulu Miao, Yunyun Lu, Yanjun Xu, Gu Zhang, Zhiyu Huang, Lei Gong, Yun Fan
BACKGROUND: Blocking the binding between the PD-1 and PD-L1 has been reported to produce antitumor responses. The MET/HGF axis appears to be another signaling pathway frequently altered in small cell lung cancer (SCLC). Our study was aimed to investigate the expression and prognostic roles of PD-L1 and c-MET in SCLC. METHODS: The expression levels of PD-L1 and c-MET were evaluated by immunohistochemical analysis in 83 SCLC specimens. Survival analysis was performed using the Kaplan-Meier method...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901258/from-biology-to-therapy-improvements-of-therapeutic-options-in-lung-cancer
#10
Luigi Formisano, Valerie M Jansen, Roberta Marciano, Roberto Bianco
Lung cancer is the leading cause of cancer-related mortality around the world, despite effective chemotherapeutic agents, the prognosis has remained poor for a long time. The discovery of molecular changes that drive lung cancer has led to a dramatic shift in the therapeutic landscape of this disease. In "in vitro" and "in vivo" models of NSCLC (non-small cell lung cancer), angiogenesis blockade has demonstrated an excellent anti-tumor activity, thus, a number of anti-angiogenic drugs have been approved by regulatory authorities for use in clinical practice...
September 12, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28900290/alteration-of-pd-l1-expression-and-its-prognostic-impact-after-concurrent-chemoradiation-therapy-in-non-small-cell-lung-cancer-patients
#11
Daichi Fujimoto, Keiichiro Uehara, Yuki Sato, Ichiro Sakanoue, Munehiro Ito, Shunsuke Teraoka, Kazuma Nagata, Atsushi Nakagawa, Yasuhiro Kosaka, Kojiro Otsuka, Yukihiro Imai, Hiroshi Hamakawa, Yutaka Takahashi, Masaki Kokubo, Keisuke Tomii
Concurrent chemoradiation therapy (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD-1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CCRT on programmed cell death ligand-1 (PD-L1) expression on tumor cells is unknown. In this study, we analysed paired NSCLC specimens that had been obtained pre- and post-CCRT. PD-L1 expression on tumor cells was studied by immunohistochemistry...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894827/the-genetic-landscape-of-programmed-death-ligand-1-pd-l1-alterations-in-head-and-neck-cancer
#12
Thomas E Heineman, Adam Widman, Edward C Kuan, Maie St John
OBJECTIVES: Nivolumab has recently been shown in the phase III clinical trial CheckMate-141 to have superior survival rates compared to the current standard of care chemotherapy for recurrent or metastatic platinum-resistant head and neck squamous cell carcinoma (HNSCC). Nivolumab targets the immune inhibitory receptor programmed cell death 1 (PD-1). Programmed cell death ligand 1 (PD-L1) genomics have been poorly characterized in the context of HNSCC, including expression levels of PD-L1 in individual tumors as well as related up or down-regulated genes that might function as co-targets...
June 2017: Laryngoscope Investigative Otolaryngology
https://www.readbyqxmd.com/read/28892778/an-increase-in-bag-1-by-pd-l1-confers-resistance-to-tyrosine-kinase-inhibitor-in-non-small-cell-lung-cancer-via-persistent-activation-of-erk-signalling
#13
Po-Lin Lin, Tzu-Chin Wu, De-Wei Wu, Lee Wang, Chi-Yi Chen, Huei Lee
High programmed cell death 1 ligand 1 (PD-L1) expression in tumour tissues was associated with poor outcomes in non-small cell lung cancer (NSCLC) due to evasion of tumour immune surveillance. However, the role of PD-L1 in tumour invasion and resistance to tyrosine kinase inhibitor (TKI) treatments is not fully understood. Here, we provide evidence to support the involvement of PD-L1 expression in the invasiveness and TKI resistance in NSCLC cells by increased Bcl-2-associated athanogene-1 (BAG-1) expression...
September 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28892775/challenges-and-perspectives-in-the-immunotherapy-of-hodgkin-lymphoma
#14
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/28884747/adverse-prognostic-value-of-pd-l1-expression-in-primary-resected-pulmonary-squamous-cell-carcinomas-and-paired-mediastinal-lymph-node-metastases
#15
Manuel D Keller, Christina Neppl, Yasin Irmak, Sean R Hall, Ralph A Schmid, Rupert Langer, Sabina Berezowska
Immunohistochemical assessment of programmed cell death (PD)-ligand 1 (PD-L1) expression in lung cancer in the context of therapeutically targeting the PD1/PD-L1 axis is still controversially discussed. This includes the comparability of antibody clones, prognostic value, and discrepancies between primary tumors and metastases. We assessed tumoral PD-L1 expression using clones E1L3N and SP142 in 372 primary resected pulmonary squamous cell carcinomas, including 40 paired N2 lymph node metastases, in relation with clinico-pathological parameters...
September 8, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28881856/strategies-targeting-angiogenesis-in-advanced-non-small-cell-lung-cancer
#16
REVIEW
Jun Wang, Jianpeng Chen, Yan Guo, Baocheng Wang, Huili Chu
Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881674/prognostic-significance-of-pd-l1-expression-and-18-f-fdg-pet-ct-in-surgical-pulmonary-squamous-cell-carcinoma
#17
Minghui Zhang, Dalong Wang, Qi Sun, Haihong Pu, Yan Wang, Shu Zhao, Yan Wang, Qiangyuan Zhang
Programmed cell death-ligand 1 (PD-L1) expression is commonly observed in non-small cell lung cancer (NSCLC). The prognostic value of PD-L1 expression and the maximum standardized uptake value (SUVmax) on 18F-Fluorodeoxyglucose positron emission tomography ((18)FDG-PET) in surgical pulmonary squamous cell carcinoma(SCC)remains unclear. Furthermore, the correlation between the SUVmax and PD-L1 expression has not been assessed. Thus, the purpose of this study was to investigate the correlation between PD-L1 expression and the SUVmax on (18)FDG-PET and to examine the prognostic significance of PD-L1 expression and the SUVmax in surgical pulmonary SCC...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881488/case-series-of-pleomorphic-carcinomas-of-the-lung-treated-with-nivolumab
#18
Masaki Kanazu, Takeshi Uenami, Yukihiro Yano, Saeko Nakatsubo, Yuki Hosono, Mikako Ishijima, Yuki Akazawa, Toshihiko Yamaguchi, Koji Urasaki, Masahide Mori, Soichiro Yokota
Pleomorphic carcinoma (PC) of the lung is a rare type of non-small cell lung cancer, exhibiting aggressive behavior and resistance to chemotherapy and radiotherapy. A previous study reported that PCs expressed high levels of PD-L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumors. We retrospectively reviewed the clinical records of three patients with PC of the lung treated with nivolumab: a 59-year-old woman (Case 1), a 66-year-old man (Case 2), and an 83-year-old man (Case 3)...
September 7, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28880013/osimertinib-azd9291-decreases-programmed-death-ligand-1-in-egfr-mutated-non-small-cell-lung-cancer-cells
#19
Xiao-Ming Jiang, Yu-Lian Xu, Mu-Yang Huang, Le-Le Zhang, Min-Xia Su, Xiuping Chen, Jin-Jian Lu
Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1). Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro. Osimertinib (125 nmol/L) markedly suppressed PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28879076/immunotherapy-shock-a-case-series-of-pd-l1-100-and-pembrolizumab-first-line-treatment
#20
Paul Zarogoulidis, Evaggelia Athanasiou, Theodora Tsiouda, Dimitrios Hatzibougias, Haidong Huang, Chong Bai, Georgia Trakada, Lemonia Veletza, Anastasios Kallianos, Christoforos Kosmidis, Nikolaos Barbetakis, Dimitrios Paliouras, Aggeliki Rapti, Dimitrios Drougas, Wolfgang Hohenforst-Schmidt
In this decade a "bloom" of novel therapies has been observed for non-small cell lung cancer. We have new tools for the diagnosis of lung cancer and also we can re-biospy easier than before in different lesions and obtain tissue samples in order to investigate whether a patient can receive new targeted therapies. Immunotherapy has been well established previously for other forms of cancer, and nowadays it is also available for lung cancer. There are two immunotherapies for now nivolumab and pembrolizumab which can be administered as second line treatment, the second can also be administered as first-line if there is a programmed death-ligand 1 ≥50% expression...
2017: Respiratory Medicine Case Reports
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