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https://www.readbyqxmd.com/read/28934595/copd-alters-immune-cell-composition-and-immune-checkpoint-inhibitor-efficacy-in-nsclc
#1
Nicholas M Mark, Julia Kargl, Stephanie E Busch, Grace H Y Yang, Heather E Metz, Huajia Zhang, Jesse J Hubbard, Sudhakar N J Pipavath, David K Madtes, A McGarry Houghton
RATIONALE: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality; the pathogenesis of both involves aberrant immune functioning. OBJECTIVE: To profile the immune cell composition and function in patients with NSCLC and describe the effect of COPD on lung and tumor microenvironments. METHODS: We profiled resected lung and tumor tissue using flow cytometry and T-cell receptor sequencing in patients with and without COPD from a prospective cohort of patients undergoing resection of NSCLC...
September 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28934428/hiv-infected-children-have-elevated-levels-of-pd-1-memory-cd4-t-cells-with-low-proliferative-capacity-and-high-inflammatory-cytokine-effector-functions
#2
Julia Foldi, Lina Kozhaya, Bret McCarty, Mussa Mwamzuka, Fatma Marshed, Tiina Ilmet, Max Kilberg, Adam Kravietz, Aabid Ahmed, William Borkowsky, Derya Unutmaz, Alka Khaitan
Background: During human immunodeficiency virus (HIV) disease, chronic immune activation leads to T-cell exhaustion. PD-1 identifies "exhausted" CD8 T cells with impaired HIV-specific effector functions, but its role on CD4 T cells and in HIV-infected children is poorly understood. Methods: In a Kenyan cohort of vertically HIV-infected children, we measured PD-1+ CD4 T-cell frequencies and phenotype by flow cytometry and their correlation with HIV disease progression and immune activation...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28932641/response-to-first-line-chemotherapy-regimen-is-associated-with-efficacy-of-nivolumab-in-non-small-cell-lung-cancer
#3
Courèche-Guillaume Kaderbhai, Corentin Richard, Jean David Fumet, Anne Aarnink, Sandra Ortiz-Cuaran, Maurice Pérol, Pascal Foucher, Bruno Coudert, Laure Favier, Aurélie Lagrange, Emeric Limagne, Romain Boidot, Sylvain Ladoire, Michel Poudenx, Marius Ilie, Paul Hofman, Pierre Saintigny, François Ghiringhelli
Nivolumab, an anti PD-1 checkpoint inhibitor has demonstrated efficacy in metastatic non-small-cell lung cancer (NSCLC) patients after failure to standard chemotherapy. Standard chemotherapy agents could promote antitumor immune response. We thus examined whether the response to first line chemotherapy could impact on nivolumab benefit. One hundred and 15 patients with NSCLC were included in this retrospective study from 4 different French centers. Forty-three squamous cell carcinomas (SCC), and 72 non-SCC received nivolumab between 2015 and 2016 (3 mg/kg IV Q2W)...
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
#4
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/28932563/a-systematic-and-genome-wide-correlation-meta-analysis-of-pd-l1-expression-and-targetable-nsclc-driver-genes
#5
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/28931759/combination-immunotherapy-with-tlr-agonists-and-checkpoint-inhibitors-suppresses-head-and-neck-cancer
#6
Fumi Sato-Kaneko, Shiyin Yao, Alast Ahmadi, Shannon S Zhang, Tadashi Hosoya, Megan M Kaneda, Judith A Varner, Minya Pu, Karen S Messer, Cristiana Guiducci, Robert L Coffman, Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, Dennis A Carson, Tomoko Hayashi, Ezra Ew Cohen
Checkpoint inhibitors have demonstrated efficacy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, the majority of patients do not benefit from these agents. To improve the efficacy of checkpoint inhibitors, intratumoral (i.t.) injection with innate immune activators, TLR7 and TLR9 agonists, were tested along with programmed death-1 receptor (PD-1) blockade. The combination therapy suppressed tumor growth at the primary injected and distant sites in human papillomavirus-negative (HPV-negative) SCC7 and MOC1, and HPV-positive MEER syngeneic mouse models...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931755/combination-central-tolerance-and-peripheral-checkpoint-blockade-unleashes-antimelanoma-immunity
#7
Pearl Bakhru, Meng-Lei Zhu, Hsing-Hui Wang, Lee K Hong, Imran Khan, Maria Mouchess, Ajay S Gulati, Joshua Starmer, Yafei Hou, David Sailer, Sandra Lee, Fengmin Zhao, John M Kirkwood, Stergios Moschos, Lawrence Fong, Mark S Anderson, Maureen A Su
Blockade of immune checkpoint proteins (e.g., CTLA-4, PD-1) improves overall survival in advanced melanoma; however, therapeutic benefit is limited to only a subset of patients. Because checkpoint blockade acts by "removing the brakes" on effector T cells, the efficacy of checkpoint blockade may be constrained by the limited pool of melanoma-reactive T cells in the periphery. In the thymus, autoimmune regulator (Aire) promotes deletion of T cells reactive against self-antigens that are also expressed by tumors...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931514/melanoma-drugs-effective-as-adjuvants
#8
(no author information available yet)
BRAF-targeted strategies and PD-1-blocking immunotherapy are more effective adjuvant therapies than currently approved options for patients with high-risk resectable melanoma. However, choosing the best agent for patients with BRAF-mutated disease remains a challenge.
September 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28929192/role-of-pd-1-in-immunity-and-diseases
#9
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
#10
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/28928158/characterization-of-the-immune-microenvironment-in-hepatocellular-carcinoma-hcc
#11
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
https://www.readbyqxmd.com/read/28927079/new-use-of-microsatellite-instability-analysis-in-endometrial-cancer
#12
Haruko Kunitomi, Kouji Banno, Megumi Yanokura, Takashi Takeda, Moito Iijima, Kanako Nakamura, Miho Iida, Masataka Adachi, Keiko Watanabe, Yusuke Matoba, Yusuke Kobayashi, Eiichiro Tominaga, Daisuke Aoki
The increasing incidence of obesity and diabetes due to changes in diet, earlier menarche, delayed menopause, late marriage, and declining birth rate have resulted in an increase in the number of endometrial cancer cases over the last few decades. Although surgical therapy is sufficient for early endometrial cancer, there is no effective therapy for patients with advanced and recurrent endometrial cancer. The oncogenic mechanism of endometrial cancer involves microsatellite instability (MSI) caused by dysfunction of DNA mismatch repair genes in 30% of patients...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926891/-advances-in-immune-checkpoint-inhibitors-in-gastrointestinal-cancer
#13
X R Zhu, L Z Zheng
Currently, immunotherapy is considered as the fourth major modality of cancer treatment except surgery, chemotherapy and radiotherapy. The new therapeutic approach based on immune checkpoint inhibitors is a landmark innovation. Strategies considering checkpoint inhibitors have shown good anti-tumor effect by targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1). Moreover, DNA mismatch repair-deficient tumors appear to be potential candidates for these therapies...
September 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28926356/development-of-bell-s-palsy-after-treatment-with-ipilimumab-and-nivolumab-for-metastatic-melanoma-a-case-report
#14
Julia M Zecchini, Sara Kim, Kendra Yum, Philip Friedlander
Ipilimumab is a human monoclonal antibody that targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and it is FDA approved for the treatment of unresectable or metastatic melanoma. Immune-related adverse events (irAEs) of gastrointestinal, dermatologic, and endocrine origin are commonly seen, ranging between 18% and 44%, with immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1). Rare irAEs include neurological, renal, and hematologic toxicities. Bell's palsy is a form of neurological toxicity that presents as an idiopathic paralysis of the muscles on one side of the face...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#15
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28925087/relationship-of-tumor-pd-l1-cd274-expression-with-lower-mortality-in-lung-high-grade-neuroendocrine-tumor
#16
Kentaro Inamura, Yusuke Yokouchi, Maki Kobayashi, Hironori Ninomiya, Rie Sakakibara, Makoto Nishio, Sakae Okumura, Yuichi Ishikawa
Programmed death-ligand 1 (PD-L1) promotes immunosuppression by binding to PD-1 on T lymphocytes. Although tumor PD-L1 expression is a potential predictive marker of clinical response to anti-PD-1/PD-L1 therapy, little is known about its association with clinicopathological features, including prognosis, in high-grade neuroendocrine tumors (HGNETs), including small-cell lung carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC), of the lung. We immunohistochemically examined the membranous of expression of PD-L1 in 115 consecutive surgical cases of lung HGNET (74 SCLC cases and 41 LCNEC cases)...
September 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28923212/a-molecular-and-preclinical-comparison-of-the-pd-1-targeted-t-cell-checkpoint-inhibitors-nivolumab-and-pembrolizumab
#17
REVIEW
Petros Fessas, Hassal Lee, Shinji Ikemizu, Tobias Janowitz
T-cell checkpoint inhibition has a profound impact on cancer care and the programmed cell death protein 1 (PD-1)-targeted antibodies nivolumab and pembrolizumab have been two of the lead molecules of this therapeutic revolution. Their clinical comparability is a highly relevant topic of discussion, but to a significant degree is a consequence of their molecular properties. Here we provide a molecular, preclinical, and early clinical comparison of the two antibodies, based on the available data and recent literature...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28923211/nivolumab-and-pembrolizumab-monoclonal-antibodies-against-programmed-cell-death-1-pd-1-that-are-interchangeable
#18
REVIEW
Vinay Prasad, Victoria Kaestner
Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1), whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance. These drugs have earned a series of FDA approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin lymphoma, and renal cell cancer...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28923100/checkpoint-inhibitor-is-active-against-large-cell-neuroendocrine-carcinoma-with-high-tumor-mutation-burden
#19
Victoria E Wang, Anatoly Urisman, Lee Albacker, Siraj Ali, Vincent Miller, Rahul Aggarwal, David Jablons
BACKGROUND: Large cell neuroendocrine tumor (LCNEC) of the lung is a rare and aggressive tumor similar to small cell lung cancer (SCLC). Thus, it is often treated similarly to SCLC in the front-line setting with a platinum doublet. However, treatment for patients beyond the first line remains undefined. CASE PRESENTATION: We report the case of a patient with stage IB LCNEC (PD-L1 negative but positive for PD-L1 amplification and tumor mutation burden high) who progressed after adjuvant chemotherapy after surgery and subsequent therapy with an antibody drug conjugate targeting a neuroendocrine-specific cell surface marker but achieved a significant and durable response with pembrolizumab, a humanized IgG4 monoclonal anti-PD-1 antibody...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28922567/determination-of-pd-l1-expression-in-effusions-from-mesothelioma-by-immuno-cytochemical-staining
#20
Mohammed S I Mansour, Tomas Seidal, Ulrich Mager, Amir Baigi, Katalin Dobra, Annika Dejmek
BACKGROUND: Malignant mesothelioma (MM) is an aggressive, fatal tumor. Current therapeutic options only marginally improve survival. Programmed cell death ligand 1 (PD-L1) is a dominant mediator of immunosuppression, binding to programmed cell death 1 (PD-1). PD-L1 is up-regulated in cancer cells, and the PD-1/PD-L1 pathway plays a critical role in tumor immune evasion, thus providing a target for antitumor therapy. Further, a correlation between PD-L1 expression and prognosis has been reported...
September 18, 2017: Cancer
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