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PD-1 PD-L1

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https://www.readbyqxmd.com/read/28230773/programmed-death-ligand-1-pd-l1-tumor-expression-is-associated-with-a-better-prognosis-and-diabetic-disease-in-triple-negative-breast-cancer-patients
#1
Gerardo Botti, Francesca Collina, Giosuè Scognamiglio, Federica Rao, Valentina Peluso, Rossella De Cecio, Michela Piezzo, Gabriella Landi, Michelino De Laurentiis, Monica Cantile, Maurizio Di Bonito
Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28228726/current-diagnosis-and-management-of-immune-related-adverse-events-iraes-induced-by-immune-checkpoint-inhibitor-therapy
#2
REVIEW
Vivek Kumar, Neha Chaudhary, Mohit Garg, Charalampos S Floudas, Parita Soni, Abhinav B Chandra
The indications of immune checkpoint inhibitors (ICIs) are set to rise further with the approval of newer agents like tremelimumab and atezolimumab for use in patients with advanced stage mesothelioma and urothelial carcinoma respectively. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs). The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28228704/pd-1-and-pd-l1-immune-checkpoint-blockade-to-treat-breast-cancer
#3
REVIEW
Andreas D Hartkopf, Florin-Andrei Taran, Markus Wallwiener, Christina B Walter, Bernhard Krämer, Eva-Maria Grischke, Sara Y Brucker
Immune checkpoint inhibition represents a major recent breakthrough in the treatment of malignant diseases including breast cancer. Blocking the programmed death receptor-1 (PD-1) and its ligand, PD-L1, has shown impressive antitumor activity and may lead to durable long-term disease control, especially in the triple-negative subtypes of breast cancer (TNBC). Although immune checkpoint blockade is generally well tolerated, specific immune-related adverse events (irAEs) may occur. This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer...
December 2016: Breast Care
https://www.readbyqxmd.com/read/28228279/loss-of-pten-is-associated-with-resistance-to-anti-pd-1-checkpoint-blockade-therapy-in-metastatic-uterine-leiomyosarcoma
#4
Suzanne George, Diana Miao, George D Demetri, Dennis Adeegbe, Scott J Rodig, Sachet Shukla, Mikel Lipschitz, Ali Amin-Mansour, Chandrajit P Raut, Scott L Carter, Peter Hammerman, Gordon J Freeman, Catherine J Wu, Patrick A Ott, Kwok-Kin Wong, Eliezer M Van Allen
Response to immune checkpoint blockade in mesenchymal tumors is poorly characterized, but immunogenomic dissection of these cancers could inform immunotherapy mediators. We identified a treatment-naive patient who has metastatic uterine leiomyosarcoma and has experienced complete tumor remission for >2 years on anti-PD-1 (pembrolizumab) monotherapy. We analyzed the primary tumor, the sole treatment-resistant metastasis, and germline tissue to explore mechanisms of immunotherapy sensitivity and resistance...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228226/-progress-of-pd-1-pd-l1-inhibitors-in-non-small-cell-lung-cancer
#5
Zhansheng Jiang, Zhanyu Pan, Xiubao Ren
Pembrolizumab, an inhibitor target programmed death 1 (PD-1), was approved into the first line therapy in advanced non-small cell lung cancer (NSCLC). It was a milestone that immune checkpoints drugs have played an important role in the treatment system of NSCLC. The results of clinical trials revealed the superiority of PD-1/programmed death ligand 1 (PD-L1) inhibitors compared with chemotherapy in first-line, second-line and multidrug resistance phase therapy. Objective response rate (ORR) was up to 80% with pembrolizumab plus chemotherapy, and progression-free survival (PFS) with single pembrolizumab in first line was nearly 1 year (10...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28223273/pd-l1-studies-across-tumor-types-its-differential-expression-and-predictive-value-in-patients-treated-with-immune-checkpoint-inhibitors
#6
Harriet M Kluger, Christopher R Zito, Gabriela Turcu, Marina Baine, Hongyi Zhang, Adebowale Adeniran, Mario Sznol, David L Rimm, Yuval Kluger, Lieping Chen, Justine V Cohen, Lucia B Jilaveanu
PURPOSE: With recent approval of inhibitors of PD-1 in melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC), extensive efforts are underway to develop biomarkers predictive of response. PD-L1 expression has been most widely studied, and is more predictive in NSCLC than RCC or melanoma. We therefore studied differences in expression patterns across tumor types. EXPERIMENTAL DESIGN: We employed tissue microarrays with tumors from NSCLC, RCC or melanoma and a panel of cell lines to study differences between tumor types...
February 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28223102/inflammatory-cytokines-il-17-and-tnf-%C3%AE-up-regulate-pd-l1-expression-in-human-prostate-and-colon-cancer-cells
#7
Xun Wang, Lingyun Yang, Feng Huang, Qiuyang Zhang, Sen Liu, Lin Ma, Zongbing You
Programmed cell death protein 1 (PD-1) acts on PD-1 ligands (PD-L1 and PD-L2) to suppress activation of cytotoxic T lymphocytes. Interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) are co-expressed by T helper 17 (TH17) cells in many tumors. The purpose of this study was to test if IL-17 and TNF-α may synergistically induce PD-L1 expression in human prostate cancer LNCaP and human colon cancer HCT116 cell lines. We found that IL-17 did not induce PD-L1 mRNA expression, but up-regulated PD-L1 protein expression in HCT116 and LNCaP cells...
February 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28222447/impact-of-pd-l1-expression-in-patients-with-surgically-resected-non-small-cell-lung-cancer
#8
Satoshi Igawa, Yuichi Sato, Shinichiro Ryuge, Masaaki Ichinoe, Ken Katono, Yasuhiro Hiyoshi, Sakiko Otani, Ryo Nagashio, Hiroyasu Nakashima, Masato Katagiri, Jiichiro Sasaki, Yoshiki Murakumo, Yukitoshi Satoh, Noriyuki Masuda
BACKGROUND: Immunotherapy can become a crucial therapeutic option to improve the prognosis of patients with non-small-cell lung cancer (NSCLC). Here, we evaluated the impact of programmed cell death ligand-1 (PD-L1) expression in surgically resected NSCLCs. METHODS: We estimated PD-L1 expression in 229 consecutive NSCLC specimens using rabbit polyclonal antibodies to human PD-L1 in a SP263 immunohistochemical assay and evaluated PD-L1 expression for potential associations with clinicopathological parameters and survival time...
February 22, 2017: Oncology
https://www.readbyqxmd.com/read/28222333/immunoprofiling-as-a-predictor-of-patient-s-response-to-cancer-therapy-promises-and-challenges
#9
REVIEW
Daniel Bethmann, Zipei Feng, Bernard A Fox
Immune cell infiltration is common to many tumors and has been recognized by pathologists for more than 100 years. The application of digital imaging and objective assessment software allowed a concise determination of the type and quantity of immune cells and their location relative to the tumor and, in the case of colon cancer, characterized overall survival better than AJCC TNM staging. Subsequently, expression of PD-L1, by 50% or more tumor cells, identified NSCLC patients with double the response rate to anti-PD-1...
February 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28222308/comparative-analysis-of-pd-l1-expression-between-primary-and-metastatic-pulmonary-adenocarcinomas
#10
Sehui Kim, Jaemoon Koh, Dohee Kwon, Bhumsuk Keam, Heounjeong Go, Young A Kim, Yoon Kyung Jeon, Doo Hyun Chung
Programmed death-ligand 1 (PD-L1) expression in pulmonary adenocarcinomas (pADCs) was implicated in predicting anti-PD-1/PD-L1 therapy efficacy. However, the differential expression of PD-L1 between primary and metastatic pADC remains unclear. Thus, we addressed this issue. In total, 161 paired primary and metastatic tumour tissues from 146 patients with pADC were collected. Most of the cases had regional nodal metastasis (134/161, 83.2%). PD-L1 expression was categorised based on the proportion of immunostained tumour cells using cutoff values of 1%, 5%, 10% and 50%...
February 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28220772/tumour-and-host-cell-pd-l1-is-required-to-mediate-suppression-of-anti-tumour-immunity-in-mice
#11
Janet Lau, Jeanne Cheung, Armando Navarro, Steve Lianoglou, Benjamin Haley, Klara Totpal, Laura Sanders, Hartmut Koeppen, Patrick Caplazi, Jacqueline McBride, Henry Chiu, Rebecca Hong, Jane Grogan, Vincent Javinal, Robert Yauch, Bryan Irving, Marcia Belvin, Ira Mellman, Jeong M Kim, Maike Schmidt
Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication by the immune system. Therapeutic use of blocking antibodies to PD-L1 or its receptor PD-1 has produced unparalleled, durable clinical responses, with highest likelihood of response seen in patients whose tumour or immune cells express PD-L1 before therapy. The significance of PD-L1 expression in each cell type has emerged as a central and controversial unknown in the clinical development of immunotherapeutics...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28219886/dependence-of-glomerulonephritis-induction-on-novel-intraglomerular-alternatively-activated-bone-marrow-derived-macrophages-and-mac-1-and-pd-l1-in-lupus-prone-nzm2328-mice
#12
Sun-Sang J Sung, Yan Ge, Chao Dai, Hongyang Wang, Shu Man Fu, Rahul Sharma, Young S Hahn, Jing Yu, Thu H Le, Mark D Okusa, Warren K Bolton, Jessica R Lawler
Glomerular damage mediated by glomerulus-infiltrating myeloid-derived cells is a key pathogenic event in lupus nephritis (LN), but the process is poorly understood. Confocal microscopy of kidney sections and flow cytometry analysis of glomerular cells from magnetic bead-purified glomeruli have identified glomerulus-infiltrating leukocyte populations in NZM2328 (NZM) lupus-prone mice with spontaneous chronic glomerulonephritis (GN) and anti-glomerular basement membrane-induced nephritis. The occurrence of a major glomerulus-infiltrating CD11b(+)F4/80(-)I-A(-) macrophage population exhibiting the markers programmed death ligand-1 (PD-L1), Mac-2, and macrophage mannose receptor (CD206) and producing Klf4, Il10, Retnla, Tnf, and Il6 mRNA, which are known to be expressed by alternatively activated (M2b) macrophages, correlated with proteinuria status...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28219001/glut1-as-a-prognostic-factor-for-classical-hodgkin-s-lymphoma-correlation-with-pd-l1-and-pd-l2-expression
#13
Young Wha Koh, Jae-Ho Han, Seong Yong Park, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh
Background: Glucose transporter type 1 (GLUT1) expression is linked to glucose metabolism and tissue hypoxia. A recent study reported that GLUT1 was significantly associated with programmed death ligand 1 (PD-L1) as a therapeutic target in relapsed or refractory classical Hodgkin's lymphoma (cHL). The purpose of this study was to measure the expression of GLUT1 and assess its prognostic significance and potential relationships with PD-L1, programmed death ligand 2 (PD-L2), and programmed death-1 (PD-1) expressions in cHL...
February 21, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28218497/chemotherapy-induces-tumor-immune-evasion-by-upregulation-of-programmed-cell-death-ligand%C3%A2-1-expression-in-bone-marrow-stromal-cells
#14
Mengqi Yang, Panpan Liu, Kefeng Wang, Christophe Glorieux, Yumin Hu, Shijun Wen, Wenqi Jiang, Peng Huang
Programmed cell death ligand 1 (PD-L1) is a negative regulator of the immune response that enables tumor cells to escape T-cell immunity. Although PD-L1 expression in cancer cells has been extensively studied, the expression of PD-L1 in stromal cells and its clinical significance remain largely unknown. Here, we show that bone marrow stromal cells express a low level of PD-L1 and that this molecule is significantly upregulated by key drugs used in the treatment of lymphoma at clinically relevant concentrations...
December 28, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28214651/a-review-on-the-evolution-of-pd-1-pd-l1-immunotherapy-for-bladder-cancer-the-future-is-now
#15
REVIEW
Joaquin Bellmunt, Thomas Powles, Nicholas J Vogelzang
The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990. Modern immunotherapy has focused on inhibitors of checkpoint proteins, which are molecules that impede immune function, thereby allowing tumor cells to grow and proliferate unregulated...
February 2, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#16
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28213726/pd-1-and-pd-l1-antibodies-in-cancer-current-status-and-future-directions
#17
REVIEW
Arjun Vasant Balar, Jeffrey S Weber
Immunotherapy has moved to the center stage of cancer treatment with the recent success of trials in solid tumors with PD-1/PD-L1 axis blockade. Programmed death-1 or PD-1 is a checkpoint molecule on T cells that plays a vital role in limiting adaptive immune responses and preventing autoimmune and auto-inflammatory reactivity in the normal host. In cancer patients, PD-1 expression is very high on T cells in the tumor microenvironment, and PD-L1, its primary ligand, is variably expressed on tumor cells and antigen-presenting cells within tumors, providing a potent inhibitory influence within the tumor microenvironment...
February 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#18
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28213003/the-expression-of-pd-l1-protein-as-a-prognostic-factor-in-lung-squamous-cell-carcinoma
#19
Kazuki Takada, Tatsuro Okamoto, Gouji Toyokawa, 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)/programmed cell death-ligand 1 (PD-L1) pathway-targeted immunotherapy has become the standard option of care in the management of lung cancer. The expression of the PD-L1 protein in lung cancer is expected to be a prognostic factor or to predict the response to PD-1-blocking antibodies. However, the association between PD-L1 positivity and the clinicopathological features and patient outcomes in lung squamous cell carcinoma (SCC) remains unclear because the definitive cut-off value for the expression of PD-L1 protein remains to be established...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212990/high-plasma-levels-of-soluble-programmed-cell-death-ligand-1-are-prognostic-for-reduced-survival-in-advanced-lung-cancer
#20
Yusuke Okuma, Yukio Hosomi, Yoshiro Nakahara, Kageaki Watanabe, Yukiko Sagawa, Sadamu Homma
OBJECTIVES: Programmed cell death-ligand 1 (PD-L1) expressed in tumor tissues is a key molecule for immune suppression, given its role in immune checkpoints. The significance and implication of soluble PD-L1 (sPD-L1) in the blood of lung cancer patients remain unknown. PATIENTS AND METHODS: Blood samples were prospectively collected from patients with advanced lung cancer, and the plasma sPD-L1 concentrations were measured by enzyme-linked immunosorbent assay. The correlations of the plasma sPD-L1 levels with clinico-pathological status, laboratory data, and survival of the patients were analyzed...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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