keyword
MENU ▼
Read by QxMD icon Read
search

pd-l1, lung cancer

keyword
https://www.readbyqxmd.com/read/29142786/extraordinary-clinical-benefit-to-sequential-treatment-with-targeted-therapy-and-immunotherapy-of-a-braf-v600e-and-pd-l1-positive-metastatic-lung-adenocarcinoma
#1
Shuyu D Li, Annia Martial, Alexa B Schrock, Jane J Liu
Background: The treatment algorithm for metastatic non-small cell lung cancers (NSCLCs) has been evolving rapidly due to the development of new therapeutic agents. Although guidelines are provided by National Comprehensive Cancer Network (NCCN) for treatment options according to biomarker testing results, sequentially applying the three main modalities (chemotherapy, targeted therapy and immunotherapy) remains an ad hoc practice in clinic. In light of recent FDA approval of dabrafenib and trametinib combination for metastatic NSCLCs with BRAF V600E mutation, one question arises due to insufficient clinical data is if the targeted therapy should be used before immunotherapy in patients with both BRAF V600E and PD-L1 expression...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29140105/durvalumab-in-non-small-cell-lung-cancer-patients-current-developments
#2
Laura Mezquita, David Planchard
Immune checkpoint inhibitors (ICIs) are a key component of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1. Durvalumab (MEDI4736) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2. Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population. Durvalumab is under evaluation in early, locally advanced and advanced disease as monotherapy and combined with ICIs, targeted therapies, chemotherapy and radiotherapy...
November 15, 2017: Future Oncology
https://www.readbyqxmd.com/read/29137398/prognostic-significance-of-pd-l1-expression-and-tumor-infiltrating-lymphocyte-in-surgically-resectable-non-small-cell-lung-cancer
#3
Gen Lin, Xirong Fan, Weifeng Zhu, Cheng Huang, Wu Zhuang, Haipeng Xu, Xiandong Lin, Dan Hu, Yunjian Huang, Kan Jiang, Qian Miao, Chao Li
Programmed death ligand 1 (PD-L1) expression is a predictive biomarker of the success of PD-1/PD-L1 inhibitor therapy for patients with advanced non-small cell lung cancer (NSCLC) but its role as a prognostic marker for early stage resectable NSCLC remains unclear. Here, we studied PD-L1 expression and tumor infiltrating lymphocytes (TILs) in surgically resectable NSCLC and correlate the finding with clinicopathological features and patient outcomes. Total of 170 archival samples of resectable NSCLC were probed for PD-L1 expression using the clone 22C3 pharmDx kit...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135534/the-multiple-faces-of-programmed-cell-death-ligand-1-expression-in-malignant-and-nonmalignant-cells
#4
Edwin R Parra, Pamela Villalobos, Jaime Rodriguez-Canales
Preliminary data suggest that tumor expression of programmed cell death ligand 1 (PD-L1) protein in human cancers, as determined by immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples, may predict clinical response to anti-PD-1/PD-L1 therapy. PD-L1 is not a specific tumor marker and its expression is also observed in various nonmalignant cells, such as macrophages and lymphocytes, causing confusion in immunohistochemistry analysis when these inflammatory cells are overlapping with tumors cells...
November 13, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29129441/health-related-quality-of-life-results-for-pembrolizumab-versus-chemotherapy-in-advanced-pd-l1-positive-nsclc-keynote-024-a-multicentre-international-randomised-open-label-phase-3-trial
#5
Julie R Brahmer, Delvys Rodríguez-Abreu, Andrew G Robinson, Rina Hui, Tibor Csőszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O'Brien, Suman Rao, Katsuyuki Hotta, Jin Zhang, Gregory M Lubiniecki, Anne C Deitz, Reshma Rangwala, Martin Reck
BACKGROUND: In the phase 3 KEYNOTE-024 trial, treatment with pembrolizumab conferred longer progression-free survival than did platinum-based therapy in patients with treatment-naive, advanced non-small-cell lung cancer (NSCLC) with a programmed cell death-ligand 1 (PD-L1) tumour proportion score of 50% or greater (PD-L1-positive). Here we report the prespecified exploratory endpoint of pembrolizumab versus chemotherapy on patient-reported outcomes (PROs). METHODS: In this multicentre, international, randomised, open-label, phase 3 trial, we recruited patients with treatment-naive, stage IV NSCLC in 102 sites in 16 countries...
November 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29127022/genetic-and-immune-profiles-of-solid-predominant-lung-adenocarcinoma-reveal-potential-immunotherapeutic-strategies
#6
Zhong-Yi Dong, Chao Zhang, Yu-Fa Li, Jian Su, Zhi Xie, Si-Yang Liu, Li-Xu Yan, Zhi-Hong Chen, Xue-Ning Yang, Jun-Tao Lin, Hai-Yan Tu, Jin-Ji Yang, Qing Zhou, Yue-Li Sun, Wen-Zhao Zhong, Yi-Long Wu
BACKGROUND: Subtype classification of lung adenocarcinoma (LUAD) divides different survivals and therapeutic vulnerabilities, while the underlying molecular mechanism is little to be known. This study sought to determine the genetic and immune profiles of histologic subtypes and identify the evidence for adjuvant immunotherapy. PATIENTS AND METHODS: We performed an integrated analysis on multidimensional data from a discovery set including cohorts of The Cancer Genome Atlas (TCGA) and the Broad set from the LUAD public database, and a validation set from the Guangdong Lung Cancer Institute (GLCI)...
November 7, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29125731/imaging-pd-l1-expression-with-immunopet
#7
Charles Truillet, Hsueh Ling J Oh, Siok Ping Yeo, Chia-Yin Lee, Loc T Huynh, Junnian Wei, Matthew F L Parker, Collin Blakely, Natalia Sevillano, Yung-Hua Wang, Yuqin S Shen, Victor Olivas, Khaled M Jami, Anna Moroz, Benoit Jego, Emilie Jaumain, Lawrence Fong, Charles S Craik, Albert J Chang, Trever G Bivona, Cheng-I Wang, Michael J Evans
High sensitivity imaging tools could provide a more holistic view of target antigen expression to improve the identification of patients who might benefit from cancer immunotherapy. We developed for immunoPET a novel recombinant human IgG1 (termed C4) that potently binds an extracellular epitope on human and mouse PD-L1 and radiolabeled the antibody with zirconium-89. Small animal PET/CT studies showed that (89)Zr-C4 detected antigen levels on a patient derived xenograft (PDX) established from a non-small-cell lung cancer (NSCLC) patient before an 8-month response to anti-PD-1 and anti-CTLA4 therapy...
November 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29124315/the-class-i-iv-hdac-inhibitor-mocetinostat-increases-tumor-antigen-presentation-decreases-immune-suppressive-cell-types-and-augments-checkpoint-inhibitor-therapy
#8
David Briere, Niranjan Sudhakar, David M Woods, Jill Hallin, Lars D Engstrom, Ruth Aranda, Harrah Chiang, Andressa L Sodré, Peter Olson, Jeffrey S Weber, James G Christensen
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29123964/a-novel-bifunctional-anti-pd-l1-tgf-%C3%AE-trap-fusion-protein-m7824-efficiently-reverts-mesenchymalization-of-human-lung-cancer-cells
#9
Justin M David, Charli Dominguez, Kristen K McCampbell, James L Gulley, Jeffrey Schlom, Claudia Palena
Mesenchymalization is a cellular and molecular program in which epithelial cells progressively lose their well-differentiated phenotype and adopt mesenchymal characteristics. Tumor mesenchymalization occurs during the progression of cancer to metastatic disease, and is also associated with resistance to multiple therapeutics, including killing by cytotoxic immune cells. Furthermore, tumor cells can evade immune destruction by upregulating the checkpoint molecule PD-L1, and emerging research has found higher PD-L1 expression in mesenchymalized tumors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29120224/is-there-a-role-for-programmed-death-ligand-1-testing-and-immunotherapy-in-colorectal-cancer-with-microsatellite-instability-part-ii-the-challenge-of-programmed-death-ligand-1-testing-and-its-role-in-microsatellite-instability-high-colorectal-cancer
#10
Esmeralda Celia Marginean, Barbara Melosky
CONTEXT: - The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti-programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability-high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability-high CRC...
November 9, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29119407/pd-l1-testing-in-guiding-patient-selection-for-pd-1-pd-l1-inhibitor-therapy-in-lung-cancer
#11
Katerina Ancevski Hunter, Mark A Socinski, Liza C Villaruz
Immunotherapy with programmed death 1 (PD-1)- and programmed death-ligand 1 (PD-L1)-targeted monoclonal antibodies has dramatically changed the therapeutic and prognostic landscape for several types of malignancy. PD-1 and PD-L1 are immune checkpoint proteins whose binding ultimately result in T cell exhaustion and self-tolerance. Blocking this pathway 'releases the brakes' on the immune system and allows for attack of tumor cells that express PD-L1. The clinical trials that led to the US Food and Drug Administration (FDA) approval of these agents used different immunohistochemical (IHC) platforms with various PD-L1 antibodies to assess for PD-L1 expression on either tumor cells or tumor-infiltrating immune cells...
November 8, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29119113/increased-egfr-phosphorylation-correlates-with-higher-programmed-death-ligand-1-expression-analysis-of-tki-resistant-lung-cancer-cell-lines
#12
Kenichi Suda, Leslie Rozeboom, Koh Furugaki, Hui Yu, Mary Ann C Melnick, Kim Ellison, Christopher J Rivard, Katerina Politi, Tetsuya Mitsudomi, Fred R Hirsch
Despite the recent development of immunotherapies that target programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) treatment, these therapies are less effective in NSCLC patients with epidermal growth factor receptor (EGFR) mutations. However, the molecular mechanisms underlying this lower efficacy of immunotherapies in EGFR mutant lung cancers are still unclear. In this study, we analyzed PD-L1 protein expression in lung cancer cell lines with EGFR mutations prior to and after acquisition of resistance to EGFR tyrosine kinase inhibitors (TKIs)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29114547/predictive-factors-of-response-to-immunotherapy-a-review-from-the-spanish-melanoma-group-gem
#13
REVIEW
Enrique Espinosa, Ivan Márquez-Rodas, Ainara Soria, Alfonso Berrocal, Jose Luis Manzano, Maria Gonzalez-Cao, Salvador Martin-Algarra
Immunotherapy has become a key element in the treatment of several tumors, such as lung carcinoma and melanoma. Immunotherapy, unlike classical chemotherapy and targeted drugs, may yield long-term survival, even in patients who stop treatment due to toxicity. This fact has generated considerable excitement and a real shift in the paradigm of cancer treatment. However, only a small subset of patients benefit from immunotherapy. Survival curves show that most patients have progression of the disease in the first months after starting immunotherapy, followed by a slower decrease over the first 3 years, until curves reach a plateau...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29114473/immunohistochemistry-for-predictive-biomarkers-in-non-small-cell-lung-cancer
#14
REVIEW
Mari Mino-Kenudson
In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC...
October 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29114472/molecular-diagnostics-of-lung-cancer-in-the-clinic
#15
REVIEW
Lynette Sholl
According to current practice guidelines, all patients with advanced non-small cell lung cancer (NSCLC) should undergo predictive biomarker testing. For squamous cell carcinoma patients, PD-L1 immunohistochemistry is indicated to select patients for immunotherapy in the first line. For lung adenocarcinoma, all patients with advanced disease should undergo testing for epidermal growth factor receptor (EGFR) mutations, ALK and ROS1 rearrangements, and PD-L1 expression to predict response to EGFR, ALK, or ROS1 targeted inhibitors or immunotherapy, respectively...
October 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29113321/radiation-alters-pd-l1-nkg2d-ligand-levels-in-lung-cancer-cells-and-leads-to-immune-escape-from-nk-cell-cytotoxicity-via-il-6-mek-erk-signaling-pathway
#16
Ming Jing Shen, Li Jun Xu, Li Yang, Ying Tsai, Peter C Keng, Yongbing Chen, Soo Ok Lee, Yuhchyau Chen
We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29110847/symptomatic-pseudo-progression-followed-by-significant-treatment-response-in-two-lung-cancer-patients-treated-with-immunotherapy
#17
Maximilian J Hochmair, Sophia Schwab, Otto C Burghuber, Dagmar Krenbek, Helmut Prosch
In the setting of pseudo-progression in a cancer patient who receives immunotherapeutic treatment, discontinuation of therapy is recommended if the patient is symptomatic. Here, we present two patients with advanced adenocarcinoma of the lung who developed massive tumor growth after initiation of treatment with the anti-PD-1 antibody pembrolizumab. Even though clinical deterioration occurred in the form of severe dyspnea and weight loss, pembrolizumab therapy was continued, as the speed of tumor growth suggested pseudo-progression and the tumors showed marked PD-L1 expression...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29110262/mutational-diversity-of-lung-cancer-and-associated-lymph-nodes-an-exploratory-prospective-study-of-4-resected-ciiia-n2
#18
Antoine Legras, Hélène Roussel, Giuseppe Mangiameli, Alex Arame, Bertrand Grand, Ciprian Pricopi, Alain Badia, Laure Gibault, Cécile Badoual, Elizabeth Fabre, Pierre Laurent-Puig, Hélène Blons, Françoise Le Pimpec-Barthes
Mutational heterogeneity could explain different metastatic patterns among IIIA-N2 lung cancer and influence prognosis. The identification of subclonal mutations using deep sequencing to evaluate the degree of molecular heterogeneity may improve IIIA-N2 classification. The aim of this prospective study was to assess mutational and immunohistochemical characteristics in primary tumours and involved lymph nodes (LN) in operated patients. Four patients operated for primary lung carcinoma and unisite N2 mediastinal involvement were consecutively selected...
November 6, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29107330/allele-specific-hla-loss-and-immune-escape-in-lung-cancer-evolution
#19
Nicholas McGranahan, Rachel Rosenthal, Crispin T Hiley, Andrew J Rowan, Thomas B K Watkins, Gareth A Wilson, Nicolai J Birkbak, Selvaraju Veeriah, Peter Van Loo, Javier Herrero, Charles Swanton
Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity...
October 21, 2017: Cell
https://www.readbyqxmd.com/read/29101058/increased-response-rates-to-salvage-chemotherapy-administered-after-pd-1-pd-l1-inhibitors-in-patients-with-non-small-cell-lung-cancer
#20
Song Ee Park, Se Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jong-Mu Sun
INTRODUCTION: While PD-1/PD-L1 inhibitors have shown some efficacy in treating advanced non-small cell lung cancer (NSCLC), their benefits are limited to only a subset of patients. Advanced NSCLC is generally treated with a chemotherapy and immunotherapy series. Here we evaluated whether PD-1/PD-L1 inhibitors affect the anti-tumor effects of salvage chemotherapy administered after immunotherapy (SCAI) in patients with NSCLC. METHODS: This study included patients with available SCAI response data...
October 31, 2017: Journal of Thoracic Oncology
keyword
keyword
41024
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"