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Program death ligand 1/2

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https://www.readbyqxmd.com/read/29662549/tumour-necrosis-factor-interferon-gamma-and-interleukins-as-predictive-markers-of-antiprogrammed-cell-death-protein-1-treatment-in-advanced-non-small-cell-lung-cancer-a-pragmatic-approach-in-clinical-practice
#1
Efimia Boutsikou, Kalliopi Domvri, Georgia Hardavella, Dora Tsiouda, Konstantinos Zarogoulidis, Theodoros Kontakiotis
Background: The emergence of novel antiprogrammed cell death protein-1 (PD-1) inhibitors in non-small cell lung cancers (NSCLC) has revolutionized the therapeutic landscape of this disease. Although overall survival (OS) has improved in the first- and second-line therapy settings for advanced NSCLC, the benefit is not universal. In a climate of global scrutiny for healthcare costs and potential for toxicities related to immunotherapy, appropriate patient selection is crucial. The aim of this study was to evaluate potential prognostic and predictive biomarkers interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and a panel of interleukins (ILs) in the peripheral blood, and assess any correlation with response to anti-PD-1 inhibition, progression-free survival and OS in NSCLC patients...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29658856/pembrolizumab-plus-chemotherapy-in-metastatic-non-small-cell-lung-cancer
#2
Leena Gandhi, Delvys Rodríguez-Abreu, Shirish Gadgeel, Emilio Esteban, Enriqueta Felip, Flávia De Angelis, Manuel Domine, Philip Clingan, Maximilian J Hochmair, Steven F Powell, Susanna Y-S Cheng, Helge G Bischoff, Nir Peled, Francesco Grossi, Ross R Jennens, Martin Reck, Rina Hui, Edward B Garon, Michael Boyer, Belén Rubio-Viqueira, Silvia Novello, Takayasu Kurata, Jhanelle E Gray, John Vida, Ziwen Wei, Jing Yang, Harry Raftopoulos, M Catherine Pietanza, Marina C Garassino
Background First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial. Methods In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy...
April 16, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29658848/neoadjuvant-pd-1-blockade-in-resectable-lung-cancer
#3
Patrick M Forde, Jamie E Chaft, Kellie N Smith, Valsamo Anagnostou, Tricia R Cottrell, Matthew D Hellmann, Marianna Zahurak, Stephen C Yang, David R Jones, Stephen Broderick, Richard J Battafarano, Moises J Velez, Natasha Rekhtman, Zachary Olah, Jarushka Naidoo, Kristen A Marrone, Franco Verde, Haidan Guo, Jiajia Zhang, Justina X Caushi, Hok Yee Chan, John-William Sidhom, Robert B Scharpf, James White, Edward Gabrielson, Hao Wang, Gary L Rosner, Valerie Rusch, Jedd D Wolchok, Taha Merghoub, Janis M Taube, Victor E Velculescu, Suzanne L Topalian, Julie R Brahmer, Drew M Pardoll
Background Antibodies that block programmed death 1 (PD-1) protein improve survival in patients with advanced non-small-cell lung cancer (NSCLC) but have not been tested in resectable NSCLC, a condition in which little progress has been made during the past decade. Methods In this pilot study, we administered two preoperative doses of PD-1 inhibitor nivolumab in adults with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC. Nivolumab (at a dose of 3 mg per kilogram of body weight) was administered intravenously every 2 weeks, with surgery planned approximately 4 weeks after the first dose...
April 16, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29658845/nivolumab-plus-ipilimumab-in-lung-cancer-with-a-high-tumor-mutational-burden
#4
Matthew D Hellmann, Tudor-Eliade Ciuleanu, Adam Pluzanski, Jong Seok Lee, Gregory A Otterson, Clarisse Audigier-Valette, Elisa Minenza, Helena Linardou, Sjaak Burgers, Pamela Salman, Hossein Borghaei, Suresh S Ramalingam, Julie Brahmer, Martin Reck, Kenneth J O'Byrne, William J Geese, George Green, Han Chang, Joseph Szustakowski, Prabhu Bhagavatheeswaran, Diane Healey, Yali Fu, Faith Nathan, Luis Paz-Ares
Background Nivolumab plus ipilimumab showed promising efficacy for the treatment of non-small-cell lung cancer (NSCLC) in a phase 1 trial, and tumor mutational burden has emerged as a potential biomarker of benefit. In this part of an open-label, multipart, phase 3 trial, we examined progression-free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden (≥10 mutations per megabase). Methods We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy...
April 16, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29619420/changes-in-natural-killer-cells-and-exhausted-memory-regulatory-t-cells-with-corticosteroid-therapy-in-acute-autoimmune-hepatitis
#5
Hannah C Jeffery, Manjit K Braitch, Chris Bagnall, James Hodson, Louisa E Jeffery, Rebecca E Wawman, Lin Lee Wong, Jane Birtwistle, Helen Bartlett, Ansgar W Lohse, Gideon M Hirschfield, Jessica Dyson, David Jones, Stefan G Hubscher, Paul Klenerman, David H Adams, Ye H Oo
Autoimmune hepatitis (AIH) is an immune-mediated liver disease currently treated by immunosuppressive medications with significant side effects. Thus, novel mechanistic treatments are greatly needed. We performed prospective deep immunophenotyping of blood immune cells in patients with acute AIH before and after corticosteroid therapy. Blood samples from 26 patients with acute AIH (United Kingdom-AIH Consortium) were phenotyped by flow cytometry at baseline and 4 months after starting corticosteroids. Pretreatment liver tissues were stained for forkhead box P3-positive (FOXP3POS ) regulatory T cells (Tregs), clusters of differentiation (CD)56POS natural killer (NK) cells, and chemokine (C-X-C motif) ligand 10...
April 2018: Hepatology communications
https://www.readbyqxmd.com/read/29616562/avelumab-a-review-of-its-application-in-metastatic-merkel-cell-carcinoma
#6
Jocelyn Joseph, Chrystia Zobniw, Jennifer Davis, Jaime Anderson, Van Anh Trinh
OBJECTIVE: To summarize the clinical development of avelumab and its clinical relevance in metastatic Merkel cell carcinoma (MCC). DATA SOURCES: An English-language literature search using PubMed was performed using the terms avelumab, anti-PD-1, anti-PD-L1, and MCC from January of 1950 to March 2018. Data were also obtained from package inserts, meeting abstracts, and clinical registries. STUDY SELECTION/DATA EXTRACTION: All relevant published articles of avelumab were reviewed...
April 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29616018/induction-of-interleukin-10-producing-dendritic-cells-as-a-tool-to-suppress-allergen-specific-t-helper-2-responses
#7
REVIEW
Stefan Schülke
Dendritic cells (DCs) are gatekeepers of the immune system that control induction and polarization of primary, antigen-specific immune responses. Depending on their maturation/activation status, the molecules expressed on their surface, and the cytokines produced DCs have been shown to either elicit immune responses through activation of effector T cells or induce tolerance through induction of either T cell anergy, regulatory T cells, or production of regulatory cytokines. Among the cytokines produced by tolerogenic DCs, interleukin 10 (IL-10) is a key regulatory cytokine limiting und ultimately terminating excessive T-cell responses to microbial pathogens to prevent chronic inflammation and tissue damage...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29615076/use-of-the-tumor-infiltrating-cd8-to-foxp3-lymphocyte-ratio-in-predicting-treatment-responses-to-combination-therapy-with-pertuzumab-trastuzumab-and-docetaxel-for-advanced-her2-positive-breast-cancer
#8
Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Katsuyuki Takahashi, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators...
April 3, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29615063/prediction-of-treatment-responses-to-neoadjuvant-chemotherapy-in-triple-negative-breast-cancer-by-analysis-of-immune-checkpoint-protein-expression
#9
Yuka Asano, Shinichiro Kashiwagi, Wataru Goto, Koji Takada, Katsuyuki Takahashi, Tamami Morisaki, Hisakazu Fujita, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: "Avoiding immune destruction" has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer. METHODS: A total of 177 patients with resectable early-stage breast cancer were treated with NAC...
April 4, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29614306/the-prognostic-role-of-programmed-cell-death-ligand-1-expression-in-non-small-cell-lung-cancer-patients-an-updated-meta-analysis
#10
Guangzhi Ma, Yunfu Deng, Hai Jiang, Wen Li, Qiang Wu, Qinghua Zhou
BACKGROUND: Programmed cell death-ligand 1 (PD-L1) seemed to be associated with the outcomes of non-small cell lung cancer. However the prognostic role of PD-L1 expression among NSCLC remained unclear and inconsistent. The aim of the study set out to evaluate the correlation between PD-L1 expression and the prognosis of patients that developed NSCLC. METHODS: Identified literatures were extracted of various electronic databases and a meta-analysis was performed to evaluate the prognostic role of PD-L1 among NSCLC patients...
March 31, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29602174/expression-of-programmed-death-ligand-1-is-associated-with-poor-prognosis-in-myeloid-sarcoma-patients
#11
Keisuke Kawamoto, Hiroaki Miyoshi, Takaharu Suzuki, Junichi Kiyasu, Shintaro Yokoyama, Yuya Sasaki, Hirohito Sone, Masao Seto, Jun Takizawa, Koichi Ohshima
Myeloid sarcoma (MS) is a rare condition and is an extramedullary tumour of immature myeloid cells. It is now known that the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway suppresses the host antitumor responses and that these products are expressed on both tumour cells and tumour-infiltrating cells in various malignancies. However, little is known about the significance of PD-1/PD-L1 expression on tumour cells and tumour microenvironmental cells in MS. To investigate the clinicopathological significance of PD-1/PD-L1 expression in MS, we analyzed 98 patients by immunohistochemistry...
March 30, 2018: Hematological Oncology
https://www.readbyqxmd.com/read/29600072/aberrant-status-and-clinicopathologic-characteristic-associations-of-11-target-genes-in-1-321-chinese-patients-with-lung-adenocarcinoma
#12
Mengnan Zhao, Cheng Zhan, Ming Li, Xiaodong Yang, Xinyu Yang, Yong Zhang, Miao Lin, Yifeng Xia, Mingxiang Feng, Qun Wang
Background: The aberrant status of target genes and their associations with clinicopathologic characteristics are still unclear in primary lung adenocarcinoma. Methods: The common mutations and translocations of nine target genes were evaluated in 1,247 specimens of surgically-resected primary lung adenocarcinoma. Immunohistochemistry was used to analyze the expressions of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) in 731 specimens. The frequency of the aberrations and their associations with clinicopathologic characteristics were analyzed...
January 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29599916/pd-l1-expression-and-presence-of-tils-in-small-intestinal-neuroendocrine-tumours
#13
Angela Lamarca, Daisuke Nonaka, Wolfgang Breitwieser, Garry Ashton, Jorge Barriuso, Mairéad G McNamara, Sharzad Moghadam, Jane Rogan, Wasat Mansoor, Richard A Hubner, Christopher Clark, Bipasha Chakrabarty, Juan W Valle
Background: The extent of resistance to immune surveillance in patients with well-differentiated (Wd) (grade 1/2) small-intestinal neuroendocrine tumours (Si-NETs) is unknown. Methods: Patients diagnosed with Wd Si-NETs (excluding appendix, which are considered to have a different biology to other midgut NETs) were eligible. Tumoural programmed death (PD)-ligand(L) 1 (PD-L1)/PD-L2/PD-1 and tumour infiltrating lymphocytes (TILs) [presence and phenotype] were analysed in archival tissue by immunohistochemistry (IHC); reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used for confirmation of IHC results...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29599344/racial-disparities-in-the-molecular-landscape-of-cancer
#14
Elisabeth I Heath, Filipa Lynce, Joanne Xiu, Angela Ellerbrock, Sandeep K Reddy, Elias Obeid, Stephen V Liu, Aliccia Bollig-Fischer, Duska Separovic, Ari Vanderwalde
BACKGROUND/AIM: African Americans (AA) have the highest incidence and mortality of any racial/ethnic group in the US for most cancer types. Heterogeneity in the molecular biology of cancer, as a contributing factor to this disparity, is poorly understood. To address this gap in knowledge, we explored the molecular landscape of colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and high-grade glioma (HGG) from 271 AA and 636 Caucasian (CC) cases. MATERIALS AND METHODS: DNA from formalin-fixed paraffin-embedded tumors was sequenced using next-generation sequencing...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29598887/expression-of-programmed-cell-death-1-programmed-cell-death-ligand-1-in-the-tumor-microenvironments-of-primary-gastrointestinal-diffuse-large-b-cell-lymphomas
#15
Yang Liu, Jing Ma, Kangjie Yu, Mingyang Li, Fang Liu, Qingguo Yan, Zhe Wang, Shuangping Guo
BACKGROUND: Gastrointestinal diffuse large B cell lymphoma (GI DLBCL) is the most common gastrointestinal lymphoma. However, there has not been a comprehensive investigation into the expression patterns of programmed cell death 1 (PD-1) and programmed cell death ligand 1(PD-L1) in GI DLBCL tissues. METHODS: PD-1 protein expression in tumor-infiltrating lymphocytes (TILs) was evaluated by immunohistochemical staining, and expression of PD-L1 was evaluated by using PD-L1/PAX5 immunohistochemical double staining in 92 GI DLBCL specimens...
March 12, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29596910/intrinsic-and-extrinsic-regulation-of-pd-l2-expression-in-oncogene-driven-non-small-cell-lung-cancer
#16
Daisuke Shibahara, Kentaro Tanaka, Eiji Iwama, Naoki Kubo, Keiichi Ota, Koichi Azuma, Taishi Harada, Jiro Fujita, Yoichi Nakanishi, Isamu Okamoto
INTRODUCTION: The interaction of programmed cell death-ligand 2 (PD-L2) with programmed cell death-1 (PD-1) is implicated in tumor immune escape. The regulation of PD-L2 expression in tumor cells has remained unclear, however. We here examined intrinsic and extrinsic regulation of PD-L2 expression in non-small cell lung cancer (NSCLC). METHODS: PD-L2 expression was evaluated by reverse transcription and real-time polymerase chain reaction analysis and by flow cytometry...
March 26, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29596308/ep4-as-a-therapeutic-target-for-aggressive-human-breast-cancer
#17
REVIEW
Mousumi Majumder, Pinki Nandi, Ahmed Omar, Kingsley Chukwunonso Ugwuagbo, Peeyush K Lala
G-protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G-protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions, as well as in the pathology of many diseases, including cancer progression and metastasis...
March 29, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29593889/immunotherapy-combination-strategies-non-chemotherapy-in-non-small-cell-lung-cancer
#18
REVIEW
Sandrine Niyongere, Andreas Saltos, Jhanelle E Gray
Immune checkpoint inhibitors enhance the activation and antitumor activity of the immune system, resulting in durable response rates in a select group of patients. Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1) and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of T-cell effector function. These therapeutic drugs were originally evaluated in patients with metastatic melanoma before expansion to all tumor types, including non-small cell lung cancer (NSCLC) with promising results...
February 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29593736/type-i-interferon-independent-dendritic-cell-priming-and-antitumor-t-cell-activation-induced-by-a-mycoplasma-fermentans-lipopeptide
#19
Yohei Takeda, Masahiro Azuma, Kenji Funami, Hiroaki Shime, Misako Matsumoto, Tsukasa Seya
Mycoplasma fermentans -derived diacylated lipoprotein M161Ag (MALP404) is recognized by human/mouse toll-like receptor (TLR) 2/TLR6. Short proteolytic products including macrophage-activating lipopeptide 2 (MALP2) have been utilized as antitumor immune-enhancing adjuvants. We have chemically synthesized a short form of MALP2 named MALP2s ( S -[2,3-bis(palmitoyloxy)propyl]-CGNNDE). MALP2 and MALP2s provoke natural killer (NK) cell activation in vitro but only poorly induce tumor regression using in vivo mouse models loading NK-sensitive tumors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29584546/nivolumab-for-relapsed-refractory-classic-hodgkin-lymphoma-after-failure-of-autologous-hematopoietic-cell-transplantation-extended-follow-up-of-the-multicohort-single-arm-phase-ii-checkmate-205-trial
#20
Philippe Armand, Andreas Engert, Anas Younes, Michelle Fanale, Armando Santoro, Pier Luigi Zinzani, John M Timmerman, Graham P Collins, Radhakrishnan Ramchandren, Jonathon B Cohen, Jan Paul De Boer, John Kuruvilla, Kerry J Savage, Marek Trneny, Margaret A Shipp, Kazunobu Kato, Anne Sumbul, Benedetto Farsaci, Stephen M Ansell
Purpose Genetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts. Methods This multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)-naïve (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C)...
March 27, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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