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"EGFR", "PD-L1"

Ettore D'Argento, Sabrina Rossi, Giovanni Schinzari, Antonia Strippoli, Michele Basso, Alessandra Cassano, Carlo Barone
New treatments-as immunotherapies and new antiangiogenic agents-are now available in second-line setting for patients affected by EGFR wild-type and ALK-negative non-small-cell lung cancer (NSCLC). Nintedanib, ramucirumab, nivolumab and pembrolizumab have to be included in the therapeutic sequences for patients affected by NSCLC, but no clear selection criteria are to date offered, except for patients with PD-L1 expression ≥50 %. Performance status, smoking habits and comorbidities should be considered as clinical criteria in order to select the appropriate treatment, but also tumour characteristics as histotype, platinum resistance and rapid progression after a first-line therapy should be taken into account...
December 2016: Current Treatment Options in Oncology
Corey J Langer, Shirish M Gadgeel, Hossein Borghaei, Vassiliki A Papadimitrakopoulou, Amita Patnaik, Steven F Powell, Ryan D Gentzler, Renato G Martins, James P Stevenson, Shadia I Jalal, Amit Panwalkar, James Chih-Hsin Yang, Matthew Gubens, Lecia V Sequist, Mark M Awad, Joseph Fiore, Yang Ge, Harry Raftopoulos, Leena Gandhi
BACKGROUND: Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer (NSCLC) setting. The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy. We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC...
October 10, 2016: Lancet Oncology
Kentaro Inamura, Yusuke Yokouchi, Maki Kobayashi, Rie Sakakibara, Hironori Ninomiya, Sophia Subat, Hiroko Nagano, Kimie Nomura, Sakae Okumura, Tomoko Shibutani, Yuichi Ishikawa
OBJECTIVES: Compared with non-smoking counterparts, smoking-associated lung cancers have a higher mutational load, resulting in the creation of more tumor neoantigens and increased immunogenicity. B7-H3 (also known as CD276) belongs to a family of immune modulators that includes PD-1 and PD-L1 (also known as B7-H1 or CD274). Considering the evidence that PD-L1 inhibitors have been shown to be more effective against lung cancer in smokers, we herein examined the prognostic interaction of tumor B7-H3 expression level with smoking history in lung adenocarcinoma patients...
October 1, 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Patrick H Lizotte, Elena V Ivanova, Mark M Awad, Robert E Jones, Lauren Keogh, Hongye Liu, Ruben Dries, Christina Almonte, Grit S Herter-Sprie, Abigail Santos, Nora B Feeney, Cloud P Paweletz, Meghana M Kulkarni, Adam J Bass, Anil K Rustgi, Guo-Cheng Yuan, Donald W Kufe, Pasi A Jänne, Peter S Hammerman, Lynette M Sholl, F Stephen Hodi, William G Richards, Raphael Bueno, Jessie M English, Mark A Bittinger, Kwok-Kin Wong
BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC)...
September 8, 2016: JCI Insight
Sherif Abdelhamed, Keisuke Ogura, Satoru Yokoyama, Ikuo Saiki, Yoshihiro Hayakawa
While cancer development and progression can be controlled by cytotoxic T cells, it is also known that tumor-specific CD8(+)T cells become functionally impaired by acquiring a group of inhibitory receptors known as immune checkpoints. Amongst those, programmed death-1 (PD-1) is one of the most recognized negative regulators of T cell function. In non-small lung cancers (NSCLCs), the aberrant activation of epidermal growth factor receptor (EGFR) is known to induce PD-L1 expression and further the treatment with gefitinib, a tyrosine kinase inhibitor (TKI) for EGFR, decrease the expression of PD-L1 on NSCLC...
2016: Journal of Cancer
H Kadara, M Choi, J Zhang, E P Cuentas, J R Canales, S G Gaffney, Z Zhao, C Behrens, J Fujimoto, C Chow, Y Yoo, N Kalhor, C Moran, D Rimm, S Swisher, D L Gibbons, J Heymach, E Kaftan, J P Townsend, T J Lynch, J Schlessinger, J Lee, R P Lifton, I I Wistuba, R S Herbst
BACKGROUND: Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable to lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses of a unique set of clinically annotated early-stage LUADs to better understand the pathogenesis of this disease and identify clinically relevant molecular markers. METHODS: We performed WES of 108 paired stage I-III LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B) were profiled by imaging-based immunohistochemistry in a subset of LUADs (n=92)...
September 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
W Zhang, Q Pang, S F Yu, Z Yuan, P Wang, Z Xiao
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
G Santabarbara, P Maione, A Rossi, G Palazzolo, C Gridelli
INTRODUCTION: Lung cancers remain the principal cause of death cancer-related worldwide with a poor survival rate at five years from diagnosis. In patients with NSCLC harboring specific genetic alterations the anti EGFR TKIs and the ALK TKIs have improved the response rate and the quality of life compared to standard platinum-based chemotherapy. New approaches possibly applicable at the major of patients are needed. AREAS COVERED: The discovery that the immune system plays a fundamental role in the fight against cancer...
September 23, 2016: Expert Review of Clinical Pharmacology
Steffen Filskov Sorensen, Christina Demuth, Britta Weber, Boe Sandahl Sorensen, Peter Meldgaard
OBJECTIVES: The central immune co-inhibitory programmed cell death receptor/ligand 1 (PD-1/PD-L1) pathway plays a key role in tumor immune evasion in non-small cell lung cancer (NSCLC). Soluble PD-1 (sPD-1) can be detected in the blood, and preclinical evidence suggests that sPD-1 blocks PD-1/-L1 interaction and improves anti-tumor immunity. The present study compares the concentration of sPD-1 in the serum of advanced NSCLC patients with Epidermal Growth Factor Receptor (EGFR) mutation prior to erlotinib treatment and at the time of progression and correlates these results to patient outcome...
October 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Mitsunori Higuchi, Yuki Owada, Takuya Inoue, Yuzuru Watanabe, Takumi Yamaura, Mitsuro Fukuhara, Takeo Hasegawa, Hiroyuki Suzuki
BACKGROUND: Nivolumab, an immune checkpoint inhibitor, is recently clinically applied to non-small cell lung cancer (NSCLC) treatment, and this causes T cell activation and T cell infiltration to tumor tissue through the blockade of the interaction between programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1). 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) sometimes shows false positive because of the recruitment of neutrophils, lymphocytes, and macrophages...
September 5, 2016: World Journal of Surgical Oncology
Fang Zhou, Andre L Moreira
Context .- In the burgeoning era of molecular genomics, immunoperoxidase (IPOX) testing grows increasingly relevant as an efficient and effective molecular screening tool. Patients with lung carcinoma may especially benefit from the use of IPOX because most lung carcinomas are inoperable at diagnosis and only diagnosed by small tissue biopsy or fine-needle sampling. When such small specimens are at times inadequate for molecular testing, positive IPOX results still provide actionable information. Objective ...
September 2, 2016: Archives of Pathology & Laboratory Medicine
Tiffany G Huynh, Vicente Morales-Oyarvide, Meghan J Campo, Justin F Gainor, Emine Bozkurtlar, Hironori Uruga, Ling Zhao, Maria Gomez-Caraballo, Aaron N Hata, Eugene J Mark, Michael Lanuti, Jeffrey A Engelman, Mari Mino-Kenudson
INTRODUCTION: Programmed cell death ligand 1 (PD-L1) expression on tumor cells can be upregulated via activation of CD8(+) cytotoxic T lymphocytes (CTLs) or the T helper cell (Th1) pathway, counterbalancing the CTL/Th1 microenvironment. However, PD-L1 expression in association with subtypes of tumor-associated lymphocytes and molecular alterations has not been well characterized in lung adenocarcinomas. METHODS: PD-L1 expression was evaluated in 261 resected lung adenocarcinomas using tissue microarrays and various scoring systems, and was correlated with clinicopathologic/molecular features, including the extent/subtype of tumor-associated lymphocytes (i...
August 24, 2016: Journal of Thoracic Oncology
Paul C Barnfield, Peter M Ellis
Platinum-based doublet chemotherapy with or without bevacizumab is the standard of care for the initial management of advanced and metastatic non-small cell lung cancer (NSCLC) without a targetable molecular abnormality. However, the majority of patients with NSCLC will ultimately develop resistance to initial platinum-based chemotherapy, and many remain candidates for subsequent lines of therapy. Randomised trials over the past 10-15 years have established pemetrexed (non-squamous histology), docetaxel, erlotinib and gefitinib as approved second-line agents in NSCLC without targetable driver mutations or rearrangements...
September 2016: Drugs
Haiying Cheng, Murali Janakiram, Alain Borczuk, Juan Lin, Wanglong Qiu, Huijie Liu, Jordan Chinai, Balazs Halmos, Roman Perez-Soler, Xingxing Zang
PURPOSE: Immunotherapy with antibodies against B7/CD28 family members, including PD-1, PD-L1, and CTLA-4 has shifted the treatment paradigm for non-small-cell lung carcinoma (NSCLC) with improved clinical outcome. HHLA2 is a newly discovered member of the family. By regulating T-cell function, HHLA2 could contribute to tumor immune suppression and thus be a novel target for cancer immunotherapy. There is limited information and critical need to characterize its expression profile and clinical significance in NSCLC...
August 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yufan Yang, ZhaoFei Pang, Nan Ding, Wei Dong, Wei Ma, Yun Li, Jiajun Du, Qi Liu
BACKGROUND: This systematic analysis aims to assess the efficacy of PD-1/PD-L1 blockades compared with non-PD-1/PD-L1 therapy and investigate the potential predictive factors in epithelial carcinoma patients. RESULTS: A total of 11 trials with 6716 patients of melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) were included. The pooled HRs (95%CI) were 0.67 (0.62, 0.73), p < 0.001 for OS and 0.66 (0.57, 0.76), p < 0.001 for PFS. In subgroup analyses, HRs were 0...
August 15, 2016: Oncotarget
Kentaro Inamura, Yusuke Yokouchi, Rie Sakakibara, Maki Kobayashi, Sophia Subat, Hironori Ninomiya, Hiroko Nagano, Kimie Nomura, Sakae Okumura, Yuichi Ishikawa
BACKGROUND: Programmed death-ligand 1 is an immune modulator that promotes immunosuppression by binding to programmed death-1 of T-lymphocytes. Whereas programmed death-ligand 1 expression has been shown to be associated with the clinical response to anti-programmed death-ligand 1 antibody, the association of tumor programmed death-ligand 1 expression with clinicopathological/molecular features and with prognosis remains inconclusive in lung adenocarcinoma. We therefore examined the association of programmed death-ligand 1 expression with the clinicopathological/molecular features and prognosis of lung adenocarcinoma...
October 2016: Japanese Journal of Clinical Oncology
Nan Zhang, Yuanyuan Zeng, Wenwen Du, Jianjie Zhu, Dan Shen, Zeyi Liu, Jian-An Huang
Negative regulation of the signal mediated by the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway can effectively inhibit the function of T and B cells, which play a key role in the regulation of immune response. Recently, emerging evidence has suggested that the expression of PD-L1 is related to the mutation status of the epidermal growth factor receptor (EGFR). Moreover, the activation of the EGFR signaling pathway can induce expression of PD-L1. In the present study, we demonstrated that activated EGFR can upregulate the expression of PD-L1 through the interleukin 6/Janus kinase/signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) signaling pathway in non-small cell lung cancer (NSCLC) cells...
October 2016: International Journal of Oncology
Sehui Kim, Jaemoon Koh, Moon-Young Kim, Dohee Kwon, Heounjeong Go, Young A Kim, Yoon Kyung Jeon, Doo Hyun Chung
PD-1/PD-L1-targeted immunotherapy has emerged as a promising therapeutic strategy for pulmonary adenocarcinoma (pADC). Epithelial-to-mesenchymal transition (EMT) is involved in the progression and immune evasion of cancers. Therefore, we investigated the association between PD-L1 expression and EMT phenotype in pADC. Immunohistochemistry for E-cadherin (epithelial marker), ZEB1, SNAIL, SLUG, vimentin (mesenchymal markers), PD-L1, CD8 and PD-1 was performed on 477 cases of pADC. Cases were classified into epithelial, mesenchymal, epithelial-mesenchymal, and unspecified types based on immunohistochemical results...
July 26, 2016: Human Pathology
Jin S Im, Amanda C Herrmann, Chantale Bernatchez, Cara Haymaker, Jeffrey J Molldrem, Waun Ki Hong, Roman Perez-Soler
Skin toxicity is the most common toxicity caused by Epidermal Growth Factor Receptor (EGFR) inhibitors, and has been associated with clinical efficacy. As EGFR inhibitors enhance the expression of antigen presenting molecules in affected skin keratinocytes, they may concurrently facilitate neo-antigen presentation in lung cancer tumor cells contributing to anti-tumor immunity. Here, we investigated the modulatory effect of the EGFR inhibitor, erlotinib on antigen presenting molecules and PD-L1, prominent immune checkpoint protein, of skin keratinocytes and lung cancer cell lines to delineate the link between EGFR signaling pathway inhibition and potential anti-tumor immunity...
2016: PloS One
Xiaoli Jia, Liping Zhang, Wei Wu, Wei Zhang, Chunyan Wu
Synchronous double primary lung cancer (SDPLC) is detected more frequently than in the past. However, the genetic features, diagnosis, and outcome are not well known. For diagnostic and management applications, we collected 110 lesions from 55 patients who underwent surgical resection to analyze the 5 known driver mutations (EGFR, KRAS, BRAF, EML4-ALK, and ROS1) and programmed cell death ligand 1 (PD-L1) expression in various histologic types of SDPLC. Among 110 tumor lesions, 55 (50%) tumors were found harboring EGFR mutations...
July 19, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
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