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Programmed cell death ( PD-1 )

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https://www.readbyqxmd.com/read/28551624/immunoregulatory-function-of-lymphatic-endothelial-cells-in-tumor-draining-lymph-nodes-of-human-gastric-cancer
#1
Mao Tokumoto, Hiroaki Tanaka, Yukie Tauchi, Tatsuro Tamura, Takahiro Toyokawa, Kenjiro Kimura, Kazuya Muguruma, Masakazu Yashiro, Kiyoshi Maeda, Kosei Hirakawa, Masaichi Ohira
BACKGROUND/AIM: Lymph node metastasis is the most important prognostic factor for patients with gastric cancer. Increasing evidence suggests that lymphatic endothelial cells (LECs) regulate immune responses. The aim of this study was to examine the effect of LECs on the activation of CD4(+) T cells. MATERIALS AND METHODS: We examined the impact of cancer cells on the phenotype and production of cytokines of LECs derived from tumor-draining lymph nodes. RESULTS: We showed that LECs inhibited CD4(+) T cell production of cytokines, such as IL-2, IL-10, and INF-γ...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28551033/the-molecular-signature-of-murine-t-cell-homeostatic-proliferation-reveals-both-inflammatory-and-immune-inhibition-patterns
#2
Karen A Fortner, Jeffrey P Bond, James W Austin, Jeremy M Boss, Ralph C Budd
T lymphocyte homeostatic proliferation, driven by the engagement of T cell antigen receptor with self-peptide/major histocompatibility complexes, and signaling through the common γ-chain-containing cytokine receptors, is critical for the maintenance of the T cell compartment and is regulated by the Fas death receptor (Fas, CD95). In the absence of Fas, Fas-deficient lymphoproliferation spontaneous mutation (lpr) mice accumulate homeostatically expanded T cells. The functional consequences of sequential rounds of homeostatic expansion are not well defined...
May 24, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28549836/heterogeneity-of-tumor-and-immune-cell-pd-l1-expression-and-lymphocyte-counts-in-surgical-nsclc-samples
#3
David Casadevall, Sergi Clavé, Álvaro Taus, Max Hardy-Werbin, Pedro Rocha, Marta Lorenzo, Silvia Menéndez, Marta Salido, Joan Albanell, Lara Pijuan, Edurne Arriola
BACKGROUND: Immune-checkpoint inhibitors against programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have shown remarkable therapeutic activity in non-small-cell lung cancer (NSCLC). However, biomarker-based patient selection remains a challenge. Our aim was to assess the heterogeneity of various immune markers between different tumor areas of surgically resected NSCLC specimens. MATERIALS AND METHODS: We included 94 adenocarcinoma (ADC) and 50 squamous cell carcinoma (SCC) specimens...
May 4, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28549039/paired-comparison-of-pd-l1-expression-on-cytologic-and-histologic-specimens-from-malignancies-in-the-lung-assessed-with-pd-l1-ihc-28-8pharmdx-and-pd-l1-ihc-22c3pharmdx
#4
Birgit G Skov, Torsten Skov
BACKGROUND: Programmed cell death ligand-1 (PD-L1) expression is a predictive biomarker for anti-PD-1 immunotherapy in non-small cell lung cancer. Different immunohistochemistry (IHC) assays have been developed on histologic material with different cutoffs for positivity. More than one third of the patients are diagnosed on cytology alone. We hypothesized that cytologic cell block material is suitable for PD-L1 analysis. MATERIALS AND METHODS: Eighty-six paired samples of malignancies from the lung where cytologic cell block and histologic material were available from the same lesion were stained with PD-L1 IHC 28-8pharmDx and PD-L1 IHC 22C3pharmDx...
May 25, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28546884/in-vivo-and-in-situ-programming-of-tumor-immunity-by-combining-oncolytics-and-pd-1-immune-checkpoint-blockade
#5
Eric Bartee, Zihai Li
Blockade of the programmed cell death protein 1 (PD1) pathway is clinically effective against human cancers. Although multiple types of malignancies have been shown to respond to PD1 agents, only a small percentage of patients typically benefit from this treatment. In addition, PD1 therapy often causes serious immune-related adverse events. A recent study demonstrated that local, intra-tumoral, administration of modified oncolytic myxoma virus which expresses a truncated version of the PD1 protein resulted in both increased efficacy and reduced toxicity in a clinically relevant melanoma model...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28546779/emerging-treatment-options-for-the-management-of-hodgkin-s-lymphoma-clinical-utility-of-nivolumab
#6
REVIEW
David A Bond, Lapo Alinari
Classical Hodgkin's lymphoma (cHL) is a B-cell malignancy comprised of pathologic Reed Sternberg cells with a surrounding immune-tolerant inflammatory milieu. RS cells evade immune recognition in part through programmed death ligand 1 (PD-L1) overexpression, which is genetically programmed through copy number alterations, polysomy, and amplification of the 9p24.1 locus encoding PD-L1. By engaging with PD-1+ T-cells, PD-L1 delivers a potent immune suppressive signal promoting immunologic escape of the tumor cell...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28546465/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#7
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
May 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28545581/increased-serum-level-of-soluble-interleukin-2-receptor-is-associated-with-a-worse-response-of-metastatic-clear-cell-renal-cell-carcinoma-to-interferon-alpha-and-sequential-vegf-targeting-therapy
#8
Akinori Nukui, Akinori Masuda, Hideyuki Abe, Kyoko Arai, Ken-Ichiro Yoshida, Takao Kamai
BACKGROUND: Renal cell carcinoma (RCC) is a tumor with immunogenic properties. Soluble interleukin-2 receptor (sIL-2R) has a role in T cell activation and may be important for immune regulation in various conditions, including infections, transplantation rejection, autoimmune inflammatory states, and cancer. We investigated the prognostic value of the serum sIL-2R level in patients with metastatic RCC receiving IFN-alpha and vascular endothelial growth factor (VEGF)-targeting therapy...
May 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28545567/cancer-immunotherapy-by-targeting-immune-checkpoints-mechanism-of-t-cell-dysfunction-in-cancer-immunity-and-new-therapeutic-targets
#9
REVIEW
Hwei-Fang Tsai, Ping-Ning Hsu
Immune checkpoints or coinhibitory receptors, such as cytotoxic T lymphocyte antigen (CTLA)-4 and programmed death (PD)-1, play important roles in regulating T cell responses, and they were proven to be effective targets in treating cancer. In chronic viral infections and cancer, T cells are chronically exposed to persistent antigen stimulation. This is often associated with deterioration of T cell function with constitutive activation of immune checkpoints, a state called 'exhaustion', which is commonly associated with inefficient control of tumors and persistent viral infections...
May 25, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28544595/severe-cytokine-release-syndrome-in-a-patient-receiving-pd-1-directed-therapy
#10
Seth J Rotz, Daniel Leino, Sara Szabo, Jennifer L Mangino, Brian K Turpin, Joseph G Pressey
Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors is an approach to antitumor immune system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment with anti-PD-1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin-6 inhibitor tocilizumab and corticosteroids...
May 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28544524/increase-of-cells-expressing-pd-1-and-pd-l1-and-enhancement-of-ifn-%C3%AE-production-via-pd-1-pd-l1-blockade-in-bovine-mycoplasmosis
#11
Shinya Goto, Satoru Konnai, Tomohiro Okagawa, Asami Nishimori, Naoya Maekawa, Satoshi Gondaira, Hidetoshi Higuchi, Masateru Koiwa, Motoshi Tajima, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
INTRODUCTION: Bovine mycoplasma, chiefly Mycoplasma bovis, is a pathogen that causes pneumonia, mastitis, arthritis, and otitis media in cattle. This pathogen exerts immunosuppressive effects, such as the inhibition of interferon production. However, the mechanisms involved in bovine mycoplasmosis have not been fully elucidated. In this study, we investigated the role of the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in immunosuppression in bovine mycoplasmosis...
May 24, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28539815/increase-of-soluble-programmed-cell-death-ligand-1-in-patients-with-chronic-hepatitis-c
#12
Satoshi Yamagiwa, Toru Ishikawa, Nobuo Waguri, Soichi Sugitani, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Shuji Terai
Objectives: To determine whether the soluble programmed cell death ligand 1 (sPD-L1) levels in patients with chronic hepatitis C (CHC) are associated with the clinical features of the disease and the efficacy of treatment, including interferon (IFN)-α. Methods: We investigated the sPD-L1 levels in the sera of 80 genotype 1b Japanese patients with CHC who underwent 12 weeks of telaprevir (TVR)- or simeprevir (SMV)-based triple therapy followed by 12 weeks of dual therapy with pegylated IFN-α plus ribavirin...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28539588/cooperation-of-oncolytic-herpes-virotherapy-and-pd-1-blockade-in-murine-rhabdomyosarcoma-models
#13
Chun-Yu Chen, Pin-Yi Wang, Brian Hutzen, Les Sprague, Hayley M Swain, Julia K Love, Joseph R Stanek, Louis Boon, Joe Conner, Timothy P Cripe
Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539528/prospect-of-immunotherapy-for-glioblastoma-tumor-vaccine-immune-checkpoint-inhibitors-and-combination-therapy
#14
Eiichi Ishikawa, Tetsuya Yamamoto, Akira Matsumura
To date, clinical trials of various vaccine therapies using autologous tumor antigens or tumor-associated/specific antigen peptide with adjuvants have been performed to treat patients with high-grade gliomas (HGG). Furthermore, immune checkpoint pathway-targeted therapies including anti- programmed cell death 1 (PD-1) antibody have been remarkably effective in other neoplasms, and various clinical trials with anti-PD-1 antibody in patients with HGG have started to date. It is possible that up-regulation of immune checkpoint molecules in tumor tissues after vaccine therapy may be one of the mechanisms of vaccine failure...
May 24, 2017: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/28537531/clinical-features-of-nivolumab-induced-thyroiditis-a-case-series-study
#15
Ichiro Yamauchi, Yoriko Sakane, Yorihide Fukuda, Toshihito Fujii, Daisuke Taura, Masakazu Hirata, Keisho Hirota, Yohei Ueda, Yugo Kanai, Yui Yamashita, Eri Kondo, Masakatsu Sone, Akihiro Yasoda, Nobuya Inagaki
BACKGROUND: The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. It consists of the PD-1 receptor and its two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Nivolumab is an anti-PD-1 monoclonal antibody approved for malignant melanoma, advanced non-small cell lung cancer, and advanced renal cell carcinoma in Japan. Thyrotoxicosis and hypothyroidism have both been reported in international phase 3 studies and national postmarketing surveillance of nivolumab in Japan...
May 24, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28536100/depletion-of-tumor-associated-macrophages-with-a-csf-1r-kinase-inhibitor-enhances-antitumor-immunity-and-survival-induced-by-dc-immunotherapy
#16
Floris Dammeijer, Lysanne A Lievense, Margaretha E H Kaijen-Lambers, Menno van Nimwegen, Koen Bezemer, Joost P Hegmans, Thorbald van Hall, Rudi W Hendriks, Joachim G Aerts
New immunotherapeutic strategies are needed to induce effective anti-tumor immunity in all cancer patients. Malignant mesothelioma is characterized by a poor prognosis and resistance to conventional therapies. Infiltration of tumor-associated macrophages (TAM) is prominent in mesothelioma and is linked to immune suppression, angiogenesis and tumor aggressiveness. Therefore, TAM depletion could potentially reactivate anti-tumor immunity. We show that M-CSFR-inhibition using the CSF-1R kinase inhibitor PLX3397 (pexidartinib) effectively reduced numbers of TAMs, circulating nonclassical monocytes, as well as amount of neo-angiogenesis and ascites in mesothelioma mouse models, but did not improve survival...
May 23, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28534531/unravelling-the-biology-of-sclc-implications-for-therapy
#17
REVIEW
Joshua K Sabari, Benjamin H Lok, James H Laird, John T Poirier, Charles M Rudin
Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints...
May 23, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28534248/immune-checkpoint-inhibitor-therapy-what-line-of-therapy-and-how-to-choose
#18
REVIEW
Chethan Ramamurthy, James L Godwin, Hossein Borghaei
Immunotherapy is now an established part of the treatment paradigm for advanced non-small cell lung cancer (NSCLC), but the line of therapy and the sequence of agents are still in flux. In this time when much is to be learned, the optimal therapy for most patients in both the first-line and previously treated settings is in the context of a clinical trial. For standard therapy, however, there are good data to support the practice of programmed death-ligand 1 (PD-L1) testing in the front-line advanced setting and to use pembrolizumab as first-line therapy for those with ≥50% PD-L1 expression...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28532535/-tumor-associated-fibroblasts-promote-pd-l1-expression-in-lung-cancer-cells
#19
Haiyang He, Luyu Qi, Yongsheng Xiao, Yiling Hou
BACKGROUND: Tumor-associated fibroblasts (TAF) is an important part of TME, which inhibits the function of immune cells. CD8+ T cells play a significant role in tumor immunity. T-cell membrane possesses a distinct type of molecule with a negative regulatory function. Upon interaction with its corresponding ligand [programmed death factor ligand 1 (PD-L1)], programmed death factor 1 (PD-1) is activated and thus inhibits the kinase activity of T cells. This study aims to explore the possible effects of TAF on PD-L1 expression in lung cancer cells...
May 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28530662/pd-l1-inhibits-acute-and-chronic-pain-by-suppressing-nociceptive-neuron-activity-via-pd-1
#20
Gang Chen, Yong Ho Kim, Hui Li, Hao Luo, Da-Lu Liu, Zhi-Jun Zhang, Mark Lay, Wonseok Chang, Yu-Qiu Zhang, Ru-Rong Ji
Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evoked analgesia in naive mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induced mechanical allodynia...
May 22, 2017: Nature Neuroscience
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