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https://www.readbyqxmd.com/read/28938692/effectiveness-and-safety-of-pd-1-pd-l1-inhibitors-in-the-treatment-of-solid-tumors-a-systematic-review-and-meta-analysis
#1
REVIEW
Xiaohui Wang, Zhengqiang Bao, Xiaoju Zhang, Fei Li, Tianwen Lai, Chao Cao, Zhihua Chen, Wen Li, Huahao Shen, Songmin Ying
BACKGROUND: PD-1/PD-L1 inhibitors have been implicated as potentially effective anti-cancer therapies. Some clinical randomized controlled trials (RCTs) have been completed for a variety of PD-1/PD-L1 inhibitors to treat various malignancies, and more RCTs are still under way. We carried out this systematic meta-analysis to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors. METHODS: We searched PubMed, EMBASE, clinical trial registers, conference reports, and related reviews...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938671/pd-1-pd-l1-antibodies-efficacy-and-safety-versus-docetaxel-monotherapy-in-advanced-nsclc-patients-after-first-line-treatment-option-systems-assessment
#2
Qiang Su, Zhigang Sun, Chenguang Zhang, Yanli Hou, Bangwei Cao
Meta-analysis was conducted to systematically assess the effectiveness and safety of programmed cell death protein-1 or ligand-1 (PD-1 or PD-L1) antibodies versus docetaxel alone in advanced non small cell lung cancer (NSCLC). In addition, the prognostic significance of PD-L1 expression in advanced NSCLC was also investigated. 5 eligible studies including 3579 patients were identified through comprehensive search of multiple databases. The results showed that pooled hazard ratios (HR) for overall survival (OS) and progression free survival (PFS) were 0...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938660/prognostic-value-of-programmed-death-ligand-1-in-sarcoma-a-meta-analysis
#3
Zhenhua Zhu, Zheng Jin, Mei Zhang, Yajun Tang, Guang Yang, Xiaowei Yuan, Jihang Yao, Dahui Sun
BACKGROUND: The prognostic role of programmed death-ligand 1 (PD-L1) in sarcoma remains controversial. We performed a meta-analysis so as to investigate the impact of PD-L1 on clinicopathlogical findings and survival outcomes in sarcoma. MATERIALS AND METHODS: A comprehensive search in PubMed, Embase and the Cochrane Library was conducted for relevant studies. The odds ratios or hazard ratios, at 95% confidence intervals were used as measures for investigation of the correlation between PD-L1 expression and clinicopathlogical features or survival outcomes...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938609/pegylated-arginine-deiminase-can-modulate-tumor-immune-microenvironment-by-affecting-immune-checkpoint-expression-decreasing-regulatory-t-cell-accumulation-and-inducing-tumor-t-cell-infiltration
#4
Elena Brin, Katherine Wu, Hsin-Tze Lu, Yudou He, Zhaoming Dai, Wei He
PEGylated arginine deiminase (ADI-PEG 20) is being investigated in clinical studies in arginine auxotrophic cancers and is well-tolerated. The anti-tumor properties of ADI-PEG 20 have been extensively investigated - ADI-PEG 20 inhibits the growth of auxotrophic cancers in vitro and in vivo - however, its impact on immune cells is largely unknown. Here we report the potential impact of ADI-PEG 20 on the tumor immune microenvironment. ADI-PEG 20 induced immunosuppressive programmed death-ligand 1 expression on some cancer cells in vitro, but the magnitude of the increase was cell line dependent and in most relatively small...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938605/combined-prognostic-effect-of-pd-l1-expression-and-immunoscore-in-microsatellite-unstable-advanced-gastric-cancers
#5
Kyung-Ju Kim, Han Kwang Yang, Woo Ho Kim, Gyeong Hoon Kang
BACKGROUND: The aim of this study was to evaluate how programmed death-ligand-1 (PD-L1) expression is linked to the immunoscore in the context of the tumor microenvironment and to assess the differential prognostic value of PD-L1 expression according to the immunoscore in 153 patients with microsatellite instability-high (MSI-H) advanced gastric cancer (GC). RESULTS: We found that T-PD-L1 (+) and I-PD-L1 (+) were significantly associated with a high immunoscore...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938570/pd-l1-expression-as-poor-prognostic-factor-in-patients-with-non-squamous-non-small-cell-lung-cancer
#6
Cuiling Zhou, Jianjun Tang, Huanhuan Sun, Xiaobin Zheng, Zhanyu Li, Tiantian Sun, Jie Li, Shuncong Wang, Xiuling Zhou, Hongliu Sun, Zhibin Cheng, Hongyu Zhang, Haiqing Ma
OBJECTIVES: The role of programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), especially according to histologic type, remains controversial. The purpose of this study was to assess PD-L1 expression and its association with overall survival (OS) and clinicopathologic characteristics in NSCLC. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded specimens were obtained from 108 patients with surgically resected primary NSCLC. PD-L1 expression was assessed via immunohistochemistry using a histochemistry score system...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937695/trinuclear-complexes-of-palladium-ii-with-chalcogenated-n-heterocyclic-carbenes-catalysis-of-selective-nitrile-primary-amide-interconversion-and-sonogashira-coupling
#7
Pooja Dubey, Sonu Gupta, Ajai K Singh
3-Methyl-1-(2-(phenylthio/seleno)ethyl)-1H-benzo[d]imidazol-3-ium iodide (L1/L2), a precursor of sulfated/selenated N-heterocyclic carbene, was synthesized by the reaction of benzimidazole with 1,2-dichloroethane followed by treatment with PhS/SeNa and MeI. The reaction of L1/L2 with Ag2O followed by treatment with [Pd(CH3CN)2Cl2] (metal to ligand ratio 3 : 2), i.e. transmetallation, resulted in trinuclear palladium(ii) complexes [Pd3(L1/L2-HI)2(CH3CN)Cl6] (1-2). The complexes were characterized with (1)H, (13)C{(1)H} and (77)Se{(1)H} NMR (2 only), elemental analyses, HR-MS and single-crystal X-ray diffraction...
September 22, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28936553/significance-of-evaluating-tumor-infiltrating-lymphocytes-tils-and-programmed-cell-death-ligand-1-pd-l1-expression-in-breast-cancer
#8
REVIEW
Sasagu Kurozumi, Takaaki Fujii, Hiroshi Matsumoto, Kenichi Inoue, Masafumi Kurosumi, Jun Horiguchi, Hiroyuki Kuwano
The immune system affects all phases of tumor growth from initiation to progression and dissemination. Tumor-infiltrating lymphocytes (TILs) are mononuclear immune cells that infiltrate tumor tissue. Several retrospective studies have suggested the potential of TILs as a prognostic as well as predictive factor of chemotherapy in some breast cancers. On the other hand, programmed cell death protein-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) eliminate T cell activation in various types of cancers. Prospective trials to evaluate the efficacy of antibody agents to PD-1 and PD-L1 are ongoing in patients with breast cancer...
September 21, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28935974/membrane-particles-generated-from-mesenchymal-stromal-cells-modulate-immune-responses-by-selective-targeting-of-pro-inflammatory-monocytes
#9
Fabiany da C Gonçalves, Franka Luk, Sander S Korevaar, Rachid Bouzid, Ana H Paz, Carmen López-Iglesias, Carla C Baan, Ana Merino, Martin J Hoogduijn
Mesenchymal stromal cells (MSC) are a promising therapy for immunological disorders. However, culture expanded MSC are large and get trapped in the capillary networks of the lungs after intravenous infusion, where they have a short survival time. Hypothetically, living cells are a risk for tumor formation. To reduce risks associated with MSC infusion and improve the distribution in the body, we generated membrane particles (MP) of MSC and MSC stimulated with IFN-γ (MPγ). Tracking analysis and electron microscopy indicated that the average size of MP was 120 nm, and they showed a round shape...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935898/pd-l1-is-an-activation-independent-marker-of-brown-adipocytes
#10
Jessica R Ingram, Michael Dougan, Mohammad Rashidian, Marko Knoll, Edmund J Keliher, Sarah Garrett, Scott Garforth, Olga S Blomberg, Camilo Espinosa, Atul Bhan, Steven C Almo, Ralph Weissleder, Harvey Lodish, Stephanie K Dougan, Hidde L Ploegh
Programmed death ligand 1 (PD-L1) is expressed on a number of immune and cancer cells, where it can downregulate antitumor immune responses. Its expression has been linked to metabolic changes in these cells. Here we develop a radiolabeled camelid single-domain antibody (anti-PD-L1 VHH) to track PD-L1 expression by immuno-positron emission tomography (PET). PET-CT imaging shows a robust and specific PD-L1 signal in brown adipose tissue (BAT). We confirm expression of PD-L1 on brown adipocytes and demonstrate that signal intensity does not change in response to cold exposure or β-adrenergic activation...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28935250/engineered-cells-for-costimulatory-enhancement-combined-with-il-21-enhance-the-generation-of-pd-1-disrupted-ctls-for-adoptive-immunotherapy
#11
Jie Shao, Qiuping Xu, Shu Su, Fanyan Meng, Zhengyun Zou, Fangjun Chen, Juan Du, Xiaoping Qian, Baorui Liu
Blockade of the immune cell checkpoint inhibitors programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) has become a powerful tool in cancer treatment, which is effective across various solid cancer types and hematologic malignancies. Our previous studies showed that by reducing immune tolerance, clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) modified cytotoxic T lymphocytes (CTLs) rank highly in terms of immune responses and cytotoxicity. In this study, a genetically modified K562 cell line with surface expression of 4-1BBL was developed to expand PD-1-disrupted CTLs in vitro for further adoptive immunotherapy against cancer...
September 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28932643/clinical-relevance-of-tumor-infiltrating-lymphocytes-pd-l1-expression-and-correlation-with-hpv-p16-in-head-and-neck-cancer-treated-with-bio-or-chemo-radiotherapy
#12
Dan Ou, Julien Adam, Ingrid Garberis, Pierre Blanchard, France Nguyen, Antonin Levy, Odile Casiraghi, Philippe Gorphe, Ingrid Breuskin, François Janot, Stephane Temam, Jean-Yves Scoazec, Eric Deutsch, Yungan Tao
To investigate the prognostic value of tumor infiltrating lymphocytes (TILs: CD8+ and FoxP3+), and PD-L1 expression in patients with head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy combined with cisplatin (CRT) or cetuximab (BRT). Immunohistochemistry for CD8, FoxP3 was performed on pretreatment tissue samples of 77 HNSCC patients. PD-L1 results were evaluable in 38 patients. Cox regression analysis was used to analyze the correlations of these biomarkers expression with clinicopathological characteristics and treatment outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932637/muc1-c-promotes-the-suppressive-immune-microenvironment-in-non-small-cell-lung-cancer
#13
Audrey Bouillez, Dennis Adeegbe, Caining Jin, Xiufeng Hu, Ashujit Tagde, Maroof Alam, Hasan Rajabi, Kwok-Kin Wong, Donald Kufe
The cancer immune microenvironment is of importance for the effectiveness of immunotherapy; however, its dysregulation is poorly understood. The MUC1-C oncoprotein is aberrantly overexpressed in non-small cell lung cancer (NSCLC) and has been linked to the induction of PD-L1. The present work investigated the effects of targeting MUC1-C in an immuno-competent MUC1 transgenic (MUC1.Tg) mouse model. We show that Lewis Lung Carcinoma cells expressing MUC1-C (LLC/MUC1) exhibit upregulation of PD-L1 and suppression of interferon-γ (IFN-γ)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932634/pd1-positive-tumor-infiltrating-lymphocytes-are-associated-with-poor-clinical-outcome-after-pulmonary-metastasectomy-for-colorectal-cancer
#14
Dagmar Kollmann, Thomas Schweiger, Stefan Schwarz, Desislava Ignatova, Yun-Tsan Chang, Gerrit Lewik, Sebastian F Schoppmann, Wolfram Hoetzenecker, Walter Klepetko, Emmanuella Guenova, Konrad Hoetzenecker
Pulmonary metastasectomy (PM) is routinely performed in colorectal cancer (CRC) patients with oligometastatic spreading to the lungs. Patients with an aggressive tumor phenotype should be excluded from PM, since its benefit is outweighed by early tumor recurrence and impaired prognosis. Expression of PD-1 and its ligands are prognostic factors in a variety of primary tumors. However, their impact on patients' outcome in the setting of PM for CRC has not been evaluated before. 53 CRC patients with pulmonary metastases receiving PM with curative intent were included in this study...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932565/unique-distribution-of-programmed-death-ligand-1-pd-l1-expression-in-east-asian-non-small-cell-lung-cancer
#15
Yunjian Pan, Difan Zheng, Yuan Li, Xu Cai, Zongli Zheng, Yan Jin, Haichuan Hu, Chao Cheng, Lei Shen, Jian Wang, Hongbin Ji, Yihua Sun, Xiaoyan Zhou, Haiquan Chen
BACKGROUND: To determine the proportion and clinical features of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer (NSCLC). METHODS: PD-L1 expression was assessed by immunohistochemistry (IHC) and tumor proportion score (TPS) with the use of PD-L1 IHC 22C3 antibody (Dako North America) in 108 surgically resected lung squamous cell carcinomas (SCC) and 221 lung adenocarcinomas (LUADs), and was correlated with clinical variables, histologic subtypes, and common driver mutations...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28932563/a-systematic-and-genome-wide-correlation-meta-analysis-of-pd-l1-expression-and-targetable-nsclc-driver-genes
#16
Jin Li, Yaoqi Chen, Xiaoshun Shi, Xiaobing Le, Fenglan Feng, Jingyi Chen, Chengzhi Zhou, Yusong Chen, Shuai Wen, Haikang Zeng, Allen M Chen, Yu Zhang
BACKGROUND: Studies have shown that the ligand of programmed cell death protein 1 (B7-H1, CD274 or PD-L1) is related to lung cancer driver genes. Although studies have examined the association between lung cancer driver gene mutations or expression and PD-L1 expression, the present studies have not been mined the correlation systematically and genome-widely. METHODS: All relevant published PD-L1 articles with driver genes data and the RNA-seq dataset from The Cancer Genome Atlas (TCGA) were analyzed...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28929192/role-of-pd-1-in-immunity-and-diseases
#17
Kenji Chamoto, Muna Al-Habsi, Tasuku Honjo
Immunity developed to defend our bodies from foreign particles, including bacteria and viruses. Although effector cells responsible for acquired immunity, mainly T cells, and B cells, are able to distinguish self from non-self, they sometimes attack the body's tissues because of imperfect central tolerance. Several immune check points developed to limit overactivation of these cells. One of the most important immune checkpoints is programmed cell death-1 (PD-1), which is expressed mainly on activated lymphocytes...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28928380/predictors-of-responses-to-immune-checkpoint-blockade-in-advanced-melanoma
#18
N Jacquelot, M P Roberti, D P Enot, S Rusakiewicz, N Ternès, S Jegou, D M Woods, A L Sodré, M Hansen, Y Meirow, M Sade-Feldman, A Burra, S S Kwek, C Flament, M Messaoudene, C P M Duong, L Chen, B S Kwon, A C Anderson, V K Kuchroo, B Weide, F Aubin, C Borg, S Dalle, O Beatrix, M Ayyoub, B Balme, G Tomasic, A M Di Giacomo, M Maio, D Schadendorf, I Melero, B Dréno, A Khammari, R Dummer, M Levesque, Y Koguchi, L Fong, M Lotem, M Baniyash, H Schmidt, I M Svane, G Kroemer, A Marabelle, S Michiels, A Cavalcanti, M J Smyth, J S Weber, A M Eggermont, L Zitvogel
Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928286/hpv-integration-in-hnscc-correlates-with-survival-outcomes-immune-response-signatures-and-candidate-drivers
#19
Lada A Koneva, Yanxiao Zhang, Shama Virani, Pelle B Hall, Jonathan B McHugh, Douglas B Chepeha, Gregory Wolf, Thomas E Carey, Laura S Rozek, Maureen A Sartor
The incidence of human papillomavirus (HPV)-related oropharynx cancer has steadily increased over the past two decades, and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically-relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing de-escalated treatment approaches for HPV-positive HNSCC patients...
September 19, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28928158/characterization-of-the-immune-microenvironment-in-hepatocellular-carcinoma-hcc
#20
Mark Yarchoan, Dongmei Xing, Lan Luan, Haiying Xu, Rajni Sharma, Aleksandra Popovic, Timothy M Pawlik, Amy K Kim, Qingfeng Zhu, Elizabeth M Jaffee, Janis Taube, Robert A Anders
PURPOSE: Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies. EXPERIMENTAL DESIGN: To characterize the immune microenvironment in HCC, immunohistochemical (IHC) staining was performed for CD8 positive T lymphocytes, PD-1 positive and LAG-3 positive lymphocytes, CD163 positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC. RESULTS: Expression of CD8 was reduced in tumor and expression of CD163 was reduced at the tumor interface...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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