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Program death ligand 1/2

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https://www.readbyqxmd.com/read/29027395/prognostic-value-of-programmed-death-ligand-1-pd-l1-expression-in-ovarian-clear-cell-carcinoma
#1
Jun Zhu, Hao Wen, Rui Bi, Yong Wu, Xiaohua Wu
OBJECTIVE: Programmed death-ligand 1 (PD-L1) was expressed in various tumors and antibodies targeting its receptor programmed cell death-1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and its correlation with clinicopathologic features and clinical outcomes in ovarian clear cell carcinoma (OCCC). METHODS: The PD-L1 expression was measured by tissue-microarray-based immunohistochemistry from 122 eligible patients diagnosed with OCCC...
November 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/29025984/synthesis-and-biological-evaluation-of-a-novel-18-f-labeled-adnectin-as-a-pet-radioligand-for-imaging-pd-l1-expression
#2
David J Donnelly, Ralph Adam Smith, Paul Morin, Dasa Lipovsek, Jochem Gokemeijer, Daniel Cohen, Virginie Lafont, Tritin Tran, Erin Lee Cole, Martin Wright, Joonyoung Kim, Adrienne Pena, Daniel Kukral, Douglas D Dischino, Patrick Chow, Jinping Gan, Olufemi Adelakun, Xi-Tao Wang, Kai Cao, David Lueng, Samuel Bonacorsi, Wendy Hayes
The programmed death protein (PD-1) and its ligand (PD-L1) play critical roles in a checkpoint pathway cancer cells exploit to evade the immune system. A same-day PET imaging agent for measuring PD-L1 status in primary and metastatic lesions could be important for optimizing drug therapy. Herein, we have evaluated the tumor targeting of an anti-PD-L1 Adnectin after (18)F-fluorine labeling. Methods: An anti-PD-L1 Adnectin was labeled with (18)F in two steps. This synthesis featured fluorination of a novel prosthetic group, followed by a copper-free click conjugation to a modified Adnectin to generate (18)F-BMS-986192...
October 12, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28994272/programmed-death-ligand-1-expression-and-its-correlation-with-lymph-node-metastasis-in-papillary-thyroid-carcinoma
#3
Hyo Jung An, Gyung Hyuck Ko, Jeong-Hee Lee, Jong Sil Lee, Dong Chul Kim, Jung Wook Yang, Min Hye Kim, Jin Pyeong Kim, Eun Jung Jung, Dae Hyun Song
Background: The immunotherapeutic role of programmed death-ligand 1 (PD-L1) in life expectancy in many cancers has been highlighted. However, data regarding PD-L1 expression in papillary thyroid carcinoma (PTC) are limited. In this study, we describe the PD-L1 and programmed cell death protein 1 (PD-1) expressions in PTC and analyze their correlation with lymph node (LN) metastasis. Materials and Methods: Clinicopathological data were obtained from 116 patients with PTC who were treated in Gyeongsang National University Hospital, Jinju, Korea in 2009...
October 3, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28982883/programmed-cell-death-ligand-1-expression-in-primary-central-nervous-system-lymphomas-a-clinicopathological-study
#4
Azusa Hayano, Yoshihiro Komohara, Yasuo Takashima, Hiroto Takeya, Jumpei Homma, Junya Fukai, Yasuo Iwadate, Koji Kajiwara, Shin Ishizawa, Hiroaki Hondoh, Ryuya Yamanaka
BACKGROUND/AIM: Programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) have been shown to predict response to PD-L1/PD-1-targeted therapy. We analyzed PD-L1 expression in primary central nervous system lymphomas (PCNSLs). MATERIALS AND METHODS: PD-L1 protein and mRNA expression were evaluated in 64 PCNSL tissue samples. IFN-γ, IL-10, CD4, and CD8 mRNA expression was also evaluated. RESULTS: PD-L1 protein was detected in tumor cells in 2 (4...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28982752/urothelial-carcinoma-of-the-bladder-and-the-rise-of-immunotherapy
#5
REVIEW
David D Chism
With the advent of platinum-based chemotherapy, survival rates for metastatic urothelial carcinoma have plateaued, giving way to the modern immunotherapy paradigm. Although immunotherapy as an effective treatment dates back to the live, attenuated bacillus Calmette-Guérin vaccine, the recent impact of immune checkpoint inhibitors targeting programmed death/programmed death-ligand 1 (PD-1/PD-L1) coupled with the promise of both anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies and indoleamine-2, 3-dioxygenase-1 (IDO-1) inhibitors have provided a resurgence...
October 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28973656/incidence-of-endocrine-dysfunction-following-the-use-of-different-immune-checkpoint-inhibitor-regimens-a-systematic-review-and-meta-analysis
#6
Romualdo Barroso-Sousa, William T Barry, Ana C Garrido-Castro, F Stephen Hodi, Le Min, Ian E Krop, Sara M Tolaney
Importance: If not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use of immune checkpoint inhibitor (ICI) regimens are unknown. Objective: To compare the incidence and risk of endocrine AEs following treatment with US Food and Drug Administration-approved ICI regimens. Data Sources: A PubMed search through July 18, 2016, using the following keywords was performed: "ipilimumab," "MDX-010," "nivolumab," "BMS-963558," "pembrolizumab," "MK-3475," "atezolizumab," "MPDL3280A," and "phase...
September 28, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28968265/diagnostic-utility-of-pd-l1-expression-in-lung-adenocarcinoma-immunohistochemistry-and-rna-in-situ-hybridization
#7
Mohamad Mazen Gafeer, Kareem Hosny Mohammed, Claudia Ormenisan-Gherasim, Fahad Choudhary, Momin T Siddiqui, Cynthia Cohen
BACKGROUND: Programmed death receptor and programmed death ligand (PD-L1) are immunoregulatory proteins. Nonsmall cell lung cancer bypasses the immune system through the induction of protumorigenic immunosuppressive changes. The better understanding of immunology and antitumor immune responses has brought the promising development of novel immunotherapy agents like programmed death receptor checkpoint inhibitors. The aim of this study was to investigate the expression of PD-L1 in lung adenocarcinoma (ADC), comparing 2 different technologies: immunohistochemistry (IHC) by 2 methods versus RNA in situ hybridization (RISH)...
September 29, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28966619/changes-in-t-cell-and-dendritic-cell-phenotype-from-mid-to-late-pregnancy-are-indicative-of-a-shift-from-immune-tolerance-to-immune-activation
#8
Nishel Mohan Shah, Anna A Herasimtschuk, Adriano Boasso, Adel Benlahrech, Dietmar Fuchs, Nesrina Imami, Mark R Johnson
During pregnancy, the mother allows the immunologically distinct fetoplacental unit to develop and grow. Opinions are divided as to whether this represents a state of fetal-specific tolerance or of a generalized suppression of the maternal immune system. We hypothesized that antigen-specific T cell responses are modulated by an inhibitory T cell phenotype and modified dendritic cell (DC) phenotype in a gestation-dependent manner. We analyzed changes in surface markers of peripheral blood T cells, ex vivo antigen-specific T cell responses, indoleamine 2,3-dioxygenase (IDO) activity (kynurenine/tryptophan ratio, KTR), plasma neopterin concentration, and the in vitro expression of progesterone-induced blocking factor (PIBF) in response to peripheral blood mononuclear cell culture with progesterone...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28961828/nivolumab-for-relapsed-or-refractory-hodgkin-lymphoma-real-life-experience
#9
H Beköz, N Karadurmus, S Paydas, A Türker, T Toptas, T Firatli Tuglular, M Sönmez, Z Gülbas, E Tekgündüz, A H Kaya, M Özbalak, N Tastemir, L Kaynar, R Yildirim, I Karadogan, M Arat, F Pepedil Tanrikulu, V Özkocaman, H Abali, M Turgut, M Kurt Yüksel, M Özcan, M H Dogu, S Kabukçu Hacioglu, I Barista, M Demirkaya, F D Köseoglu, S K Toprak, M Yilmaz, H C Demirkürek, O Demirkol, B Ferhanoglu
Background: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. Patients and methods: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28960263/comparison-of-the-toxicity-profile-of-pd-1-versus-pd-l1-inhibitors-in-non-small-cell-lung-cancer-a-systematic-analysis-of-the-literature
#10
Rathi N Pillai, Madhusmita Behera, Taofeek K Owonikoko, Alice O Kamphorst, Suchita Pakkala, Chandra P Belani, Fadlo R Khuri, Rafi Ahmed, Suresh S Ramalingam
BACKGROUND: Monoclonal antibodies against programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are effective therapies in patients with non-small cell lung cancer (NSCLC). Herein, the authors performed a systematic review investigating differences in the toxicities of PD-1 and PD-L1 inhibitors. METHODS: An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC...
September 28, 2017: Cancer
https://www.readbyqxmd.com/read/28939128/early-immune-related-adverse-events-and-association-with-outcome-in-advanced-non-small-cell-lung-cancer-patients-treated-with-nivolumab-a-prospective-cohort-study
#11
Shunsuke Teraoka, Daichi Fujimoto, Takeshi Morimoto, Hayato Kawachi, Munehiro Ito, Yuki Sato, Kazuma Nagata, Atsushi Nakagawa, Kojiro Otsuka, Keiichiro Uehara, Yukihiro Imai, Kaori Ishida, Junya Fukuoka, Keisuke Tomii
BACKGROUND: Retrospective studies have shown immune-related adverse events (irAEs) to be associated with better prognosis. However, no prospective clinical trials have been conducted and little is known regarding the association between irAEs and the outcome of non-small cell lung cancer patients following treatment with immunotherapy. PATIENTS AND METHODS: We conducted a prospective cohort study of advanced non-small cell lung cancer patients who were treated with nivolumab between January and December 2016...
September 19, 2017: Journal of Thoracic Oncology
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
#12
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
#13
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/28923396/smac-mimetics-and-type-ii-interferon-synergistically-induce-necroptosis-in-various-cancer-cell-lines
#14
Michael John Cekay, Stefanie Roesler, Tanja Frank, Anne-Kathrin Knuth, Ines Eckhardt, Simone Fulda
Since cancer cells often evade apoptosis, induction of necroptosis as another mode of programmed cell death is considered a promising therapeutic alternative. Here, we identify a novel synergistic interaction of Smac mimetics that antagonize x-linked Inhibitor of Apoptosis (XIAP), cellular Inhibitor of Apoptosis (cIAP) 1 and 2 with interferon (IFN)γ to induce necroptosis in apoptosis-resistant cancer cells in which caspase activation is blocked. This synergism is confirmed by calculation of combination indices (CIs) and found in both solid and hematological cancer cell lines as well as for different Smac mimetics (i...
September 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28921644/clinical-pharmacology-considerations-for-the-development-of-immune-checkpoint-inhibitors
#15
Jennifer Sheng, Shivani Srivastava, Kinjal Sanghavi, Zheng Lu, Brian J Schmidt, Akintunde Bello, Manish Gupta
Immuno-oncology works through activation of the patient's immune system against cancer, with several advantages over other treatment approaches, including cytotoxic agents and molecular-targeted therapies. The most notable feature of immuno-oncology treatments is the nature of the patient responses achieved, which can be more durable and sustained than with other modalities. Increased understanding of immune system complexity has provided a number of opportunities to advance several strategies for the development of immuno-oncology therapies...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28910818/protein-expression-of-programmed-death-1-ligand-1-and-her2-in-gastric-carcinoma
#16
Eiji Oki, Shinji Okano, Hiroshi Saeki, Yuichiro Umemoto, Koji Teraishi, Yu Nakaji, Koji Ando, Yoko Zaitsu, Nami Yamashita, Masahiko Sugiyama, Yuichiro Nakashima, Kippei Ohgaki, Yoshinao Oda, Yoshihiko Maehara
OBJECTIVES: Programmed death 1 (PD-1) is an immunoinhibitory receptor and has been identified as a new target for immunotherapy in cancer. Here we report the expression of PD-1 ligand 1 (PD-L1) in surgically resected gastric cancer. MATERIALS AND METHODS: We examined formalin-fixed tumor samples from 144 gastric cancer patients with a primary diagnosis of gastric carcinoma. Immunohistochemistry was used to detect PD-L1. Human epidermal growth factor receptor 2 (HER2) expression and phosphatase and tensin homolog (PTEN) loss of heterozygosity were investigated in these patients...
September 15, 2017: Oncology
https://www.readbyqxmd.com/read/28892778/an-increase-in-bag-1-by-pd-l1-confers-resistance-to-tyrosine-kinase-inhibitor-in-non-small-cell-lung-cancer-via-persistent-activation-of-erk-signalling
#17
Po-Lin Lin, Tzu-Chin Wu, De-Wei Wu, Lee Wang, Chi-Yi Chen, Huei Lee
High programmed cell death 1 ligand 1 (PD-L1) expression in tumour tissues was associated with poor outcomes in non-small cell lung cancer (NSCLC) due to evasion of tumour immune surveillance. However, the role of PD-L1 in tumour invasion and resistance to tyrosine kinase inhibitor (TKI) treatments is not fully understood. Here, we provide evidence to support the involvement of PD-L1 expression in the invasiveness and TKI resistance in NSCLC cells by increased Bcl-2-associated athanogene-1 (BAG-1) expression...
November 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28892775/challenges-and-perspectives-in-the-immunotherapy-of-hodgkin-lymphoma
#18
REVIEW
Jean-Marie Michot, Julien Lazarovici, David Ghez, Alina Danu, Christophe Fermé, Amélie Bigorgne, Vincent Ribrag, Aurélien Marabelle, Sandrine Aspeslagh
Hodgkin lymphoma (HL) was one of the first few cancers to be cured first with radiotherapy alone and then with a combination of chemotherapy and radiotherapy. Around 80% of the patients with HL will be cured by first-line therapy. However, the ionising radiation not only produces cytotoxicity but also induces alterations in the microenvironment, and patients often struggle with the long-term consequences of these treatments, such as cardiovascular disorders, lung diseases and secondary malignancies. Hence, it is essential to improve treatments while avoiding delayed side-effects...
November 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28889792/overall-survival-with-combined-nivolumab-and-ipilimumab-in-advanced-melanoma
#19
Jedd D Wolchok, Vanna Chiarion-Sileni, Rene Gonzalez, Piotr Rutkowski, Jean-Jacques Grob, C Lance Cowey, Christopher D Lao, John Wagstaff, Dirk Schadendorf, Pier F Ferrucci, Michael Smylie, Reinhard Dummer, Andrew Hill, David Hogg, John Haanen, Matteo S Carlino, Oliver Bechter, Michele Maio, Ivan Marquez-Rodas, Massimo Guidoboni, Grant McArthur, Celeste Lebbé, Paolo A Ascierto, Georgina V Long, Jonathan Cebon, Jeffrey Sosman, Michael A Postow, Margaret K Callahan, Dana Walker, Linda Rollin, Rafia Bhore, F Stephen Hodi, James Larkin
BACKGROUND: Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial. METHODS: We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent...
October 5, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28885881/durvalumab-after-chemoradiotherapy-in-stage-iii-non-small-cell-lung-cancer
#20
Scott J Antonia, Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Takashi Yokoi, Alberto Chiappori, Ki H Lee, Maike de Wit, Byoung C Cho, Maryam Bourhaba, Xavier Quantin, Takaaki Tokito, Tarek Mekhail, David Planchard, Young-Chul Kim, Christos S Karapetis, Sandrine Hiret, Gyula Ostoros, Kaoru Kubota, Jhanelle E Gray, Luis Paz-Ares, Javier de Castro Carpeño, Catherine Wadsworth, Giovanni Melillo, Haiyi Jiang, Yifan Huang, Phillip A Dennis, Mustafa Özgüroğlu
Background Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy. Methods We randomly assigned patients, in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months...
September 8, 2017: New England Journal of Medicine
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