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pd-l1, lung cancer

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https://www.readbyqxmd.com/read/28318951/a-comprehensive-analysis-of-programmed-cell-death-ligand-1-expression-with-the-clone-sp142-antibody-in-non-small-cell-lung-cancer%C3%A2-patients
#1
Kazuki Takada, Gouji Toyokawa, Tatsuro Okamoto, Mototsugu Shimokawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Fumihiro Shoji, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND: Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with anti-PD-1 therapy currently the standard treatment for non-small-cell lung cancer (NSCLC) patients after the failure of first-line chemotherapy treatment. The recent phase II POPLAR and phase III OAK studies showed that atezolizumab, a representative PD-L1 inhibitor, exhibited a survival benefit compared with standard therapy in patients with NSCLC...
March 2, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28303311/-immunotherapy-of-cancer-with-checkpoint-inhibitors-not-only-in-malignant-melanoma
#2
A Neubauer
The newest weapon in cancer therapy is checkpoint inhibition, which is the result of basic immunology research. The success of this therapy is based on the fact that upon light microscopy, many solid tumors harbor lymphocytic cells infiltrating the tumor (TILs), and in many solid tumors, the presence of these TILs are prognostic. Ipilimumab was the first monoclonal antibody developed against a target present on T cells after becoming activated, CTLA-4. In malignant melanoma, ipilimumab showed its beneficial effect as compared to a placebo peptide...
March 16, 2017: Der Internist
https://www.readbyqxmd.com/read/28302866/genomic-profiling-of-patient-derived-xenografts-for-lung-cancer-identifies-b2m-inactivation-impairing-immunorecognition
#3
Carolina Pereira, Pol Gimenez-Xavier, Eva Pros, Maria J Pajares, Massimo Moro, Antonio Gomez, Alejandro Navarro, Enric Condom, Sebastian Moran, Gonzalo Gomez-Lopez, Osvaldo Graña, Miriam Rubio-Camarillo, Alex Martinez-Martí, Jun Yokota, Julian Carretero, Jose M Galbis, Ernest Nadal, David Pisano, Gabriella Sozzi, Enriqueta Felip, Luis M Montuenga, Luca Roz, Alberto Villanueva, Montse Sanchez-Cespedes
Purpose: We aimed to maximize the performance of detecting genetic alterations in lung cancer using high-throughput sequencing for patient-derived xenografts (PDXs).Experimental Design: We undertook an integrated RNA and whole-exome sequencing of 14 PDXs. We focused on the genetic and functional analysis of β2-microglobulin (B2M), a component of the HLA class-I complex.Results: We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance. We extended the mutational analysis of B2M to about 230 lung cancers...
March 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer 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
#4
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
#5
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/28295707/anti-pd-1-pd-l1-induced-psoriasis-from-an-oncological-perspective
#6
Juan Ruiz-Bañobre, Jorge García-González
We read with interest the letter to the editor by Bonigen et al(1) regarding the development of psoriasis during anti-programed cell death protein 1 (PD-1) therapy. The authors describe a series of 17 patients diagnosed with melanoma or lung cancer treated with anti-PD-1 drugs in first line or later. In the final analysis, they also include 4 patients previously described in the literature. This article is protected by copyright. All rights reserved.
March 10, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28293123/pembrolizumab-in-the-treatment-of-metastatic-non-small-cell-lung-cancer-patient-selection-and-perspectives
#7
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC) to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab), which is a monoclonal antibody targeting the programmed death 1 (PD-1) receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors)...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28289860/the-pd-l1-pd-1-pathway-promotes-dysfunction-but-not-exhaustion-in-tumor-responding-t-cells-from-pleural-effusions-in-lung-cancer-patients
#8
Heriberto Prado-Garcia, Susana Romero-Garcia, Alejandra Puerto-Aquino, Uriel Rumbo-Nava
Malignant pleural effusions are frequent in patients with advanced stages of lung cancer and are commonly infiltrated by lymphocytes and tumor cells. CD8+ T cells from these effusions have reduced effector functions. The programmed death receptor 1(PD-1)/programmed death ligand 1 (PD-L1) pathway is involved in T-cell exhaustion, and it might be responsible for T-cell dysfunction in lung cancer patients. Here, we show that PD-L1 is expressed on tumor cell samples from malignant effusions, on lung cancer cell lines, and, interestingly, on MRC-5 lung fibroblasts...
March 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28288138/muc1-c-integrates-pd-l1-induction-with-repression-of-immune-effectors-in-non-small-cell-lung-cancer
#9
A Bouillez, H Rajabi, C Jin, M Samur, A Tagde, M Alam, M Hiraki, T Maeda, X Hu, D Adeegbe, S Kharbanda, K-K Wong, D Kufe
Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65ZEB1 pathway and confers a poor prognosis...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28285697/immune-checkpoint-inhibition-in-first-line-treatment-of-advanced-non-small-cell-lung-cancer-patients-current-status-and-future-approaches
#10
REVIEW
J Remon, N Pardo, A Martinez-Martí, S Cedrés, A Navarro, A M Martinez de Castro, E Felip
Immune checkpoint inhibitors are considered standard second-line treatment in advanced non-small cell lung cancer patients. This strategy has also become standard in first-line setting for a subgroup of patients with strongly positive PD-L1 tumors; therefore, PD-L1 status might be considered a new biomarker that deserves upfront testing. New combinations of immune checkpoint inhibitors and with chemotherapy have been tested in first-line treatment. However, some questions remain unanswered such as the best treatment strategy or the real upfront efficacy of these therapeutic strategies in the whole lung cancer population...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28285592/successes-and-failures-what-did-we-learn-from-recent-first-line-treatment-immunotherapy-trials-in-non-small-cell-lung-cancer
#11
REVIEW
Jordi Remon, Benjamin Besse, Jean-Charles Soria
The immune checkpoint inhibitors have significantly modified the therapeutic landscape of advanced non-small cell lung cancer in second-line and, more recently, first-line settings. Because of the superior outcome with pembrolizumab as an upfront strategy, PD-L1 status should now be considered a new reflex biomarker for guiding first-line treatment in patients with advanced non-small cell lung cancer. Improved responses have also been reported with the combination of immune checkpoint inhibitors and chemotherapy as the first-line treatment; however, this strategy has not yet been validated by phase III trial data and its interplay with PD-L1 status still requires clarification...
March 13, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28278348/a-prospective-multi-institutional-pathologist-based-assessment-of-4-immunohistochemistry-assays-for-pd-l1-expression-in-non-small-cell-lung-cancer
#12
David L Rimm, Gang Han, Janis M Taube, Eunhee S Yi, Julia A Bridge, Douglas B Flieder, Robert Homer, William W West, Hong Wu, Anja C Roden, Junya Fujimoto, Hui Yu, Robert Anders, Ashley Kowalewski, Christopher Rivard, Jamaal Rehman, Cory Batenchuk, Virginia Burns, Fred R Hirsch, Ignacio I Wistuba
Importance: Four assays registered with the US Food and Drug Administration (FDA) detect programmed cell death ligand 1 (PD-L1) to enrich for patient response to anti-programmed cell death 1 and anti-PD-L1 therapies. The tests use 4 separate PD-L1 antibodies on 2 separate staining platforms and have their own scoring systems, which raises questions about their similarity and the potential interchangeability of the tests. Objective: To compare the performance of 4 PD-L1 platforms, including 2 FDA-cleared assays, 1 test for investigational use only, and 1 laboratory-developed test...
March 9, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28276698/the-role-of-checkpoint-inhibitors-immunotherapy-in-advanced-non-small-cell-lung-cancer-in-the-elderly
#13
Assunta Sgambato, Francesca Casaluce, Cesare Gridelli
Immune checkpoint inhibition is a novel treatment modality that has brought a new hope to patients with advanced NSCLC. Several molecules targeting cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 receptor/programmed death ligand-1 (PD1/PD-L1) pathways are under evaluation in NSCLC and three of them are currently approved: nivolumab and atezolizumab for advanced NSCLC after prior chemotherapy and pembrolizumab for advanced NSCLC expressing PD-L1 ≥ 1% after at least one prior chemotherapy regimen and > 50% as a first-line response...
February 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28275222/pd-1-pd-l1-protein-expression-in-non-small-cell-lung-cancer-and-their-relationship-with-tumor-infiltrating-lymphocytes
#14
Yayi He, Leslie Rozeboom, Christopher J Rivard, Kim Ellison, Rafał Dziadziuszko, Hui Yu, Caicun Zhou, Fred R Hirsch
BACKGROUND Immunotherapy targeting the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint has shown the good outcomes in non-small cell lung cancer (NSCLC). We investigated PD-1 and PD-L1 protein expression and their correlation with tumor-infiltrating lymphocytes (TILs), and association with survival in NSCLC. MATERIAL AND METHODS The expression of PD-1 (NAT105, Cell Marque) and PD-L1 (28-8, Dako) protein was assessed in 55 NSCLC cell lines by immunohistochemistry (IHC). PD-1 (NAT105, Cell Marque) and PD-L1 (22C3, Dako) protein expression was evaluated by IHC, and TIL percentage was scored, in 139 surgically resected specimens from patients with NSCLC...
March 9, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28275115/safety-and-tolerability-of-pd-1-pd-l1-inhibitors-compared-with-chemotherapy-in-patients-with-advanced-cancer-a-meta-analysis
#15
Tomohiro F Nishijima, Shlomit S Shachar, Kirsten A Nyrop, Hyman B Muss
BACKGROUND: Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy. METHODS: PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016...
March 8, 2017: Oncologist
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
#16
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
#17
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/28255028/gene-signature-driving-invasive-mucinous-adenocarcinoma-of-the-lung
#18
Minzhe Guo, Koichi Tomoshige, Michael Meister, Thomas Muley, Takuya Fukazawa, Tomoshi Tsuchiya, Rebekah Karns, Arne Warth, Iris M Fink-Baldauf, Takeshi Nagayasu, Yoshio Naomoto, Yan Xu, Marcus A Mall, Yutaka Maeda
Though invasive mucinous adenocarcinoma of the lung (IMA) is pathologically distinctive, the molecular mechanism driving IMA is not well understood, which hampers efforts to identify therapeutic targets. Here, by analyzing gene expression profiles of human and mouse IMA, we identified a Mucinous Lung Tumor Signature of 143 genes, which was unexpectedly enriched in mucin-producing gastrointestinal, pancreatic, and breast cancers. The signature genes included transcription factors FOXA3, SPDEF, HNF4A, mucins MUC5AC, MUC5B, MUC3, and an inhibitory immune checkpoint VTCN1/B7-H4 (but not PD-L1/B7-H1)...
March 2, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28252315/checkpoint-blockade-in-lung-cancer-and-mesothelioma
#19
Lysanne A Lievense, Daniel H Sterman, Robin Cornelissen, Joachim G Aerts
In the past decade, immunotherapy has emerged as a new treatment modality in cancer. The most success has been achieved with the class of checkpoint inhibitors; antibodies which unleash the anti-tumor immune response. Following the success in melanoma, numerous clinical trials are being conducted investigating checkpoint inhibitors in lung cancer and mesothelioma. The programmed death protein 1-protein death ligand 1/2 (PD-1 - PD-L1/2) pathway and cytotoxic T-lymphocyte associated protein 4 (CTLA4) are currently the most studied immunotherapeutic targets in these malignancies...
March 2, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28245875/severe-nivolumab-induced-pneumonitis-preceding-durable-clinical-remission-in-a-patient-with-refractory-metastatic-lung-squamous-cell-cancer-a-case-report
#20
Hong Li, Weijie Ma, Ken Y Yoneda, Elizabeth H Moore, Yanhong Zhang, Lee L Q Pu, Garrett M Frampton, Michael Molmen, Philip J Stephens, Tianhong Li
BACKGROUND: Programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) inhibitors have quickly become standard of care for patients with advanced non-small cell lung cancer and increasing numbers of other cancer types. In this report, we discuss the clinical history, pathological evaluation, and genomic findings in a patient with metastatic lung squamous cell cancer (SCC) who developed severe nivolumab-induced pneumonitis preceding durable clinical remission after three doses of nivolumab...
February 28, 2017: Journal of Hematology & Oncology
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