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pd-l1, lung cancer

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https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#1
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ≥50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29327044/association-of-the-lung-immune-prognostic-index-with-immune-checkpoint-inhibitor-outcomes-in-patients-with-advanced-non-small-cell-lung-cancer
#2
Laura Mezquita, Edouard Auclin, Roberto Ferrara, Melinda Charrier, Jordi Remon, David Planchard, Santiago Ponce, Luis Paz Ares, Laura Leroy, Clarisse Audigier-Valette, Enriqueta Felip, Jorge Zerón-Medina, Pilar Garrido, Solenn Brosseau, Gérard Zalcman, Julien Mazieres, Caroline Caramela, Jihene Lahmar, Julien Adam, Nathalie Chaput, Jean Charles Soria, Benjamin Besse
Importance: Derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitor (ICI) outcomes in patients with melanoma. Objective: To determine whether pretreatment dNLR and LDH are associated with resistance to ICIs in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: Multicenter retrospective study with a test (n = 161) and a validation set (n = 305) treated with programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors in 8 European centers, and a control cohort (n = 162) treated with chemotherapy only...
January 11, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29326364/inflammation-and-pd-l1-expression-in-pulmonary-neuroendocrine-tumors
#3
Atsuko Kasajima, Yuichi Ishikawa, Ayaka Iwata, Katja Steiger, Naomi Oka, Hirotaka Ishida, Akira Sakurada, Hiroyoshi Suzuki, Toru Kameya, Björn Konukiewitz, Gunter Kloppel, Yoshinori Okada, Hironobu Sasano, Wilko Weichert
In the light of novel cancer immune therapies, the status of antitumor inflammatory response and its regulation has gained much attention in patients with lung cancer. Ample datasets exist for non-small cell lung cancer, but those for pulmonary neuroendocrine tumors are scarce and controversial. Here, tumor-associated inflammation, CD8+ cell infiltration and PD-L1 status were evaluated in a cohort of 57 resected carcinoids and 185 resected neuroendocrine carcinomas of the lung (58 large cell carcinomas and 127 small cell carcinomas)...
January 11, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29322798/pd-l1-expression-can-be-regarded-as-prognostic-factor-for-survival-of-non-small-cell-lung-cancer-patients-after-chemoradiotherapy
#4
M Vrankar, M Zwitter, I Kern, K Stanic
Inoperable locally advanced non-small cell lung cancer (LA NSCLC) is treated with concurrent or sequential chemotherapy (ChT) and radiation therapy (RT). Survival rates with this treatment remains poor, reported 5-year survival is about 15%. New treatment strategies, including immunotherapy with programmed death ligand-1 (PD-L1) check point inhibitors are being investigated. The clinical significance of PD-L1 expression in tumor samples from patients with inoperable LA NSCLC who underwent concurrent chemoradiotherapy (CRT) in our institution between 2005 and 2010 was evaluated...
2018: Neoplasma
https://www.readbyqxmd.com/read/29318609/the-efficacy-and-safety-of-anti-pd-1-pd-l1-antibodies-combined-with-chemotherapy-or-ctla4-antibody-as-a-first-line-treatment-for-advanced-lung-cancer
#5
Xiaoling Xu, Zhiyu Huang, Lei Zheng, Yun Fan
Checkpoint inhibitors show promising efficacy in advanced lung cancer, especially in non-small cell lung cancer. This meta-analysis was conducted to explore the therapeutic efficacy and safety of anti-PD-1/PD-L1 antibodies combined with chemotherapy or CTLA4 antibody as first-line treatments for patients with advanced lung cancer. A systematic search was performed in databases for this system review and quantitative meta-analysis. Twelve trials were finally enrolled in the meta-analysis. Our analyses revealed that the combined overall response rate (ORR) and disease control rate (DCR) for immune checkpoint inhibitors combined with chemotherapy for the treatment of non-small cell lung cancer (NSCLC) were 47...
January 10, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29313208/perspective-on-immune-oncology-with-liquid-biopsy-peripheral-blood-mononuclear-cells-and-microbiome-with-non-invasive-biomarkers-in-cancer-patients
#6
REVIEW
A Mitsuhashi, Y Okuma
Antibodies against immune checkpoint inhibitors such as anti-programmed cell death protein 1 (PD-1) and anti-programmed death ligand 1 (PD-L1) play a key role in the treatment of advanced lung cancer. To examine the clinical benefits of these agents, preclinical and clinical studies have been conducted to identify definitive biomarkers associated with cancer status. Analysis of the blood and feces of tumor patients has attracted attention in recent studies attempting to identify non-invasive biomarkers such as cytokines, soluble PD-L1, peripheral blood mononuclear cells, and gut microbiota...
January 8, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29306075/fasn-tgf-%C3%AE-1-pd-l1-axis-contributes-to-the-development-of-resistance-to-nk-cell-cytotoxicity-of-cisplatin-resistant-lung-cancer-cells
#7
MingJing Shen, Ying Tsai, Rongying Zhu, Peter C Keng, Yongbing Chen, Yuhchyau Chen, Soo Ok Lee
Cisplatin remains the most effective therapy for non-small cell lung cancer (NSCLC). We previously have found cisplatin-resistant lung cancer cells (A549CisR and H157CisR) were more resistant to natural killer (NK) cell-mediated cytotoxicity than parental cells. We also discovered that fatty acid synthase (FASN) levels in cisplatin-resistant cells were significantly higher than parental cells. To reveal whether a link exists between the up-regulated FASN levels and higher resistance to NK cell cytotoxicity, we performed inhibition studies using a FASN inhibitor and applied the FASN knockdown approach...
January 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29303289/-small-cell-lung-cancer-epidemiology-diagnostics-and-therapy
#8
Miloš Pešek, Jan Mužík
Authors present actual overview of information on diagnostic and therapeutic procedures in small-cell lung cancer (SCLC). This highly aggressive type of lung cancer is diagnosed in 14.8 % of Czech lung cancer patients. Vast majority of those patients (87 %) suffer from advanced and metastatic disease in the time of diagnosis. In this issue are presented prognostic factors, staging diagnostic procedures and therapeutic recommendations. The backbone of actual SCLC treatment is combined chemotherapy and radiotherapy and less frequently, carefully in selected cases, surgical procedures...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29302251/immunotherapy-for-non-small-cell-lung-cancer-current-status-and-future-obstacles
#9
REVIEW
Ju Hwan Cho
Lung cancer is one of the leading causes of death worldwide. There are 2 major subtypes of lung cancer, non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Studies show that NSCLC is the more prevalent type of lung cancer that accounts for approximately 80%-85% of cases. Although, various treatment methods, such as chemotherapy, surgery, and radiation therapy have been used to treat lung cancer patients, there is an emergent need to develop more effective approaches to deal with advanced stages of tumors...
December 2017: Immune Network
https://www.readbyqxmd.com/read/29299418/pembrolizumab-in-advanced-pretreated-small-cell-lung-cancer-patients-with-pd-l1-expression-data-from-the-keynote-028-trial-a-reason-for-hope
#10
EDITORIAL
Alejandro Navarro, Enriqueta Felip
No abstract text is available yet for this article.
December 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29299417/the-reproducibility-of-pd-l1-scoring-in-lung-cancer-can-the-pathologists-do-better
#11
EDITORIAL
Giancarlo Troncone, Cesare Gridelli
No abstract text is available yet for this article.
December 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29299411/reproducibility-of-pd-l1-assessment-in-non-small-cell-lung-cancer-know-your-limits-but-never-stop-trying-to-exceed-them
#12
EDITORIAL
Marius Ilie, Paul Hofman
No abstract text is available yet for this article.
December 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29299404/evaluation-of-rare-but-severe-immune-related-adverse-effects-in-pd-1-and-pd-l1-inhibitors-in-non-small-cell-lung-cancer-a-meta-analysis
#13
Yang-Bo Hu, Qun Zhang, Hui-Juan Li, Jean Maire Michot, Hong-Bing Liu, Ping Zhan, Tang-Feng Lv, Yong Song
Background: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitor therapy is showing marked efficacy in advanced non-small cell lung cancer (NSCLC). Meanwhile, it is concomitant with distinctive immune-related adverse effects. We aim to describe the incidence of pneumonitis and other rare but severe immune-related adverse effects (IRAEs), as well as treatment related deaths. In addition, we analyze the differences in incidence of pneumonitis between PD-1 and PD-L1 inhibitors and standard-of-care chemotherapy...
December 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29296194/changes-in-pd-l1-expression-according-to-tumor-infiltrating-lymphocytes-of-acquired-egfr-tki-resistant-egfr-mutant-non-small-cell-lung-cancer
#14
Tae-Jung Kim, Soon Auck Hong, Okran Kim, Seung Joon Kim, Ji-Hyun Yang, Eun Kyo Joung, Jin-Hyoung Kang, Sook-Hee Hong
Backgrounds: EGFR-mutant non-small cell lung cancer (NSCLC) that developed acquired resistance to EGFR-tyrosine kinase (TKI) are potential candidates for programmed death 1 (PD1) inhibitor. Results: TPS≥1% for PD-L1 and low CD8 + TIL in post-TKI tumor showed a trend for a lower PFS of EGFR-TKIs (14.2 vs 9.9 months; P = 0.060) (cohort A). Only 2 of 22 specimens (9.1%) with an acquired EGFR exon 20 T790M mutation exhibited in post-TKI TPS≥50% for PD-L1. The degree in post-TKI tumor of PD-L1 expression was varied in 19 patients (40...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296193/tusc2-downregulates-pd-l1-expression-in-non-small-cell-lung-cancer-nsclc
#15
Xiaobo Cao, Yang Zhao, Jing Wang, Bingbing Dai, Emanuela Gentile, Jing Lin, Xingxiang Pu, Lin Ji, Shuhong Wu, Ismail Meraz, Mourad Majidi, Jack A Roth
Expression of the TUSC2 tumor-suppressor gene in TUSC2-deficient NSCLC cells decreased PD-L1 expression and inhibited mTOR activity. Overexpressing TUSC2 or treatment with rapamycin resulted in similar inhibition of PD-L1 expression. Both TUSC2 and rapamycin decreased p70 and SK6 phosphorylation, suggesting that TUSC2 and rapamycin share the same mTOR target. Microarray mRNA expression analysis using TUSC2-inducible H1299 showed that genes that negatively regulate the mTOR pathway were significantly upregulated by TUSC2 compared with control...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295721/down-regulation-of-microrna-135-promotes-sensitivity-of-non-small-cell-lung-cancer-to-gefitinib-by-targeting-trim16
#16
Ning Wang, Tingting Zhang
Personalized treatment targeting epidermal growth factor receptor (EGFR) becomes a promising way for treatment of non-small cell lung cancer (NSCLC). Gefitinib, a tyrosine kinases inhibitor, is the first drug for NSCLC, which easily leads to drug resistance. Our study was aimed to explore the functional role of microRNA (miR)-135 in the sensitivity to gefitinib of NSCLC cells. Expression of miR-135 in normal cells and NSCLC cells was assessed. Then, the effects of abnormally expressed miR-135 on cell viability, migration, invasion, apoptosis, sensitivity to gefitinib, and the expression levels of adhesion molecules and programmed death ligand 1 (PD-L1) were all analyzed in H1650 and H1975 cells...
January 2, 2018: Oncology Research
https://www.readbyqxmd.com/read/29290777/classifying-non-small-cell-lung-cancer-by-status-of-programmed-cell-death-ligand-1-and-tumor-infiltrating-lymphocytes-on-tumor-cells
#17
Shaohua Cui, Lili Dong, Jialin Qian, Lin Ye, Liyan Jiang
Purpose: To explore the possible correlation between programmed death ligand 1 (PD-L1)/tumor-infiltrating lymphocytes (TIL) status and clinical factors in non-small cell lung (NSCLC). Materials and Methods: A total of 126 surgical NSCLC samples with stage I to IIIA were retrospectively collected and analyzed. Immunohistochemistry (IHC) assays were used to detect PD-L1 protein expression. PD-L1 positivity on tumor cells was defined by positive tumor cell (TC) percentage using 5% cutoff value. Results: Thirty-seven patients (29...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29290267/comparative-effectiveness-of-immune-checkpoint-inhibitors-for-previously-treated-advanced-non-small-cell-lung-cancer-a-systematic-review-and-network-meta-analysis-of-3024-participants
#18
Pui San Tan, Pedro Aguiar, Benjamin Haaland, Gilberto Lopes
INTRODUCTION: Role of PD-L1 expression to guide immunotherapies in previously treated advanced NSCLC remains unclear and there is a lack of data comparing immune checkpoint inhibitors (ICIs) with each other. This network meta-analysis (NMA) aims to compare survival with ICIs to docetaxel and perform indirect comparisons between ICIs in the PD-L1 unselected population and by PD-L1 expression levels. METHODS: PubMed was searched and study screening was performed by two independent reviewers...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29290263/abundant-tumor-promoting-stromal-cells-in-lung-adenocarcinoma-with-hypoxic-regions
#19
Hiroshi Nakamura, Tomohiro Ichikawa, Shoko Nakasone, Tomohiro Miyoshi, Masato Sugano, Motohiro Kojima, Satoshi Fujii, Atsushi Ochiai, Takeshi Kuwata, Keiju Aokage, Kenji Suzuki, Masahiro Tsuboi, Genichiro Ishii
OBJECTIVES: Carbonic anhydrase IX (CAIX) is a marker of hypoxia and its expression by cancer associated fibroblasts (CAFs) was reportedly associated with the poor prognosis of lung adenocarcinoma. This study aimed to characterize the hypoxic microenvironment containing CAIX (+) CAFs. MATERIALS AND METHODS: First, we evaluated the clinicopathological significance of CAIX expression by CAFs in 3cm and above lung adenocarcinoma (n=188). We then compared the expressions of E-cadherin, ezrin, ALDH-1, CD44, EGFR, HSF-1, Glut-1, and PD-L1 in cancer cells, as well as those of CD204 and podoplanin in stromal cells between CAIX (+) CAFs and CAIX (-) CAFs cases (n=25, each)...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29290252/immune-checkpoint-inhibitors-in-epidermal-growth-factor-receptor-mutant-non-small-cell-lung-cancer-current-controversies-and-future-directions
#20
REVIEW
Ross A Soo, Sun Min Lim, Nicholas L Syn, Rebecca Teng, Richie Soong, Tony S K Mok, Byoung Chul Cho
Major advances with the development of epidermal growth factor receptor tyrosine kinase inhibitors and immune check-point inhibitors have ushered in a new era in lung cancer therapy. Whilst pre-clinical studies suggest EGFR-driven NSCLC inhibit antitumor immunity through the activation of the PD-1/PD-L1 pathway, epidemiology studies suggest EGFR mutant NSCLC are more likely to have decreased PD-L1 expression. The superiority of single agent PD-1/PD-L1 inhibitors over docetaxel in pre-treated EGFR mutant NSCLC appears to be moderated...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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