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PD-1 T cell

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https://www.readbyqxmd.com/read/28334399/association-of-hiv-status-with-local-immune-response-to-anal-squamous-cell-carcinoma-implications-for-immunotherapy
#1
Elizabeth L Yanik, Genevieve J Kaunitz, Tricia R Cottrell, Farah Succaria, Tracee L McMiller, Maria L Ascierto, Jessica Esandrio, Haiying Xu, Aleksandra Ogurtsova, Toby Cornish, Evan J Lipson, Suzanne L Topalian, Eric A Engels, Janis M Taube
Importance: The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28332580/clinical-impact-of-single-nucleotide-polymorphism-in-pd-l1-on-response-to-nivolumab-for-advanced-non-small-cell-lung-cancer-patients
#2
Takashi Nomizo, Hiroaki Ozasa, Takahiro Tsuji, Tomoko Funazo, Yuto Yasuda, Hironori Yoshida, Yoshitaka Yagi, Yuichi Sakamori, Hiroki Nagai, Toyohiro Hirai, Young Hak Kim
This study was intended to determine the efficacy of nivolumab, we evaluated treatment response with respect to PD-1/PD-L1 SNPs among patients with NSCLC. A total of 50 patients with NSCLC were treated with nivolumab and were also evaluated for PD-1/PD-L1 single nucleotide polymorphisms (SNPs) from plasma DNA. We investigated the association among PD-1/PD-L1 SNPs, objective response rate (ORR) and progression-free survival (PFS). Two of seven SNPs studied showed association with ORR and PFS, with maximum evidence at the marker rs2282055...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331165/tim-3-and-pd-1-regulate-cd8-t-cell-function-to-maintain-early-pregnancy-in-mice
#3
Yuan-Yuan Xu, Song-Cun Wang, Yi-Kong Lin, Da-Jin Li, Mei-Rong DU
During pregnancy, CD8(+) T cells are important regulators in the balance of fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are well-recognized negative co-stimulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that CD8(+) T cells co-expressing Tim-3 and PD-1 were down-regulated in the deciduae of female mice in abortion-prone matings compared with normal pregnant mice. In addition to their reduced numbers, the Tim-3(+)PD-1(+)CD8(+) T cells produced lower levels of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, as well as a higher level of the pro-inflammatory cytokine interferon (IFN)-γ, relative to those from normal pregnancy...
March 23, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28327551/genomic-reprograming-analysis-of-the-mesothelial-to-mesenchymal-transition-identifies-biomarkers-in-peritoneal-dialysis-patients
#4
Vicente Ruiz-Carpio, Pilar Sandoval, Abelardo Aguilera, Patricia Albar-Vizcaíno, María Luisa Perez-Lozano, Guadalupe T González-Mateo, Adrián Acuña-Ruiz, Jesús García-Cantalejo, Pedro Botías, María Auxiliadora Bajo, Rafael Selgas, José Antonio Sánchez-Tomero, Jutta Passlick-Deetjen, Dorothea Piecha, Janine Büchel, Sonja Steppan, Manuel López-Cabrera
Peritoneal dialysis (PD) is an effective renal replacement therapy, but a significant proportion of patients suffer PD-related complications, which limit the treatment duration. Mesothelial-to-mesenchymal transition (MMT) contributes to the PD-related peritoneal dysfunction. We analyzed the genetic reprograming of MMT to identify new biomarkers that may be tested in PD-patients. Microarray analysis revealed a partial overlapping between MMT induced in vitro and ex vivo in effluent-derived mesothelial cells, and that MMT is mainly a repression process being higher the number of genes that are down-regulated than those that are induced...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326889/aquaporin-4-autoimmunity-in-patients-with-systemic-lupus-erythematosus-a-predominantly-population-based-study
#5
Nasrin Asgari, Sven Jarius, Helle Laustrup, Hanne Pb Skejoe, Soeren T Lillevang, Brian G Weinshenker, Anne Voss
BACKGROUND: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Co-existence of NMOSD with systemic lupus erythematosus (SLE) putatively suggests susceptibility to antibody-mediated autoimmune disease. OBJECTIVE: To estimate the prevalence of NMOSD in SLE and investigate the immunogenetic background for an association of NMOSD and SLE...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28325750/molecular-pathways-evaluating-the-potential-for-b7-h4-as-an-immunoregulatory-target
#6
Heather L MacGregor, Pamela S Ohashi
With the clinical success of CTLA-4 and PD-1 blockade in treating malignancies, there is tremendous interest in finding new ways to augment anti-tumor responses by targeting other inhibitory molecules. In this review, we describe one such molecule. B7-H4, a member of the B7 family of immunoregulatory proteins, inhibits T cell proliferation and cytokine production through ligation of an unknown receptor expressed by activated T cells. Notably, B7-H4 protein expression is observed in a high proportion of patients' tumors across a wide variety of malignancies...
March 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#7
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28323631/search-for-unconventional-superconductors-among-the-y-i-te-i-sub-2-sub-si-sub-2-sub-compounds-i-te-i-cr-co-ni-rh-pd-pt
#8
Adam P Pikul, Malgorzata Samsel-Czekala, Grzegorz Chajewski, Tetiana Romanova, Alicja Hackemer, Roman Gorzelniak, Piotr Wiśniewski, Dariusz Kaczorowski
Motivated by the recent discovery of exotic superconductivity in YFe<sub>2</sub>Ge<sub>2</sub> we undertook reinvestigation of formation and physical properties of yttrium-based 1:2:2 silicides. Here we report on syntheses and crystal structures of the Y<i>TE</i><sub>2</sub>Si<sub>2</sub> compounds with <i>TE</i> = Cr, Co, Ni, Rh, Pd, and Pt, and their low-temperature physical properties measurements, supplemented by results of fully relativistic FPLO band structure calculations...
March 21, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/28323141/mechanistic-and-pharmacologic-insights-on-immune-checkpoint-inhibitors
#9
REVIEW
Randy F Sweis, Jason J Luke
The concept of augmenting the immune system to eradicate cancer dates back at least a century. A major resurgence in cancer immunotherapy has occurred over the past decade since the identification and targeting of negative regulators with antibody therapies to augment the anti-tumor immune response. Unprecedented responses across a broad array of cancer types elevated this class of therapies to the forefront of cancer treatment. The most successful drugs to date target the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28322160/an-efficient-transient-expression-system-for-enhancing-generation-of-monoclonal-antibodies-in-293-suspension-cells
#10
Guoquan Zhang, Jie Liu, Wanting Fan, Qianyi Chen, Bin Shi
BACKGROUND: Recombinant monoclonal antibodies (mAbs) are useful in research, diagnosis, and therapy. The increased demands of recombinant mAbs require efficient production systems. A variety of expression vectors have been developed for stable or transient production of mAb in mammalian cells. However, though a few commercial expression systems of mAbs can be listened, the high expense often impedes academia researches. METHODS: In this study, we described the development of a transient mammalian system based on a bicistronic vector, which contains internal ribosome entry site (IRES) and enhancer elements to express IgG1 light chain (LC) and heavy chain (HC) in one transcript...
March 20, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28321813/harnessing-the-immune-system-against-leukemia-monoclonal-antibodies-and-checkpoint-strategies-for-aml
#11
Lucia Masarova, Hagop Kantarjian, Guillermo Garcia-Mannero, Farhad Ravandi, Padmanee Sharma, Naval Daver
Acute myeloid leukemia (AML) is the most common leukemia among adults and is associated with a poor prognosis, especially in patients with adverse prognostic factors, older age, or relapsed disease. The last decade has seen a surge in successful immune-based therapies in various solid tumors; however, the role of immune therapies in AML remains poorly defined. This chapter describes the rationale, clinical data, and toxicity profiles of immune-based therapeutic modalities in AML including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, chimeric antigen receptor (CAR)-T cells, and checkpoint blockade via blockade of PD1/PDL1 or CTLA4...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#12
Alix Besançon, Marije Baas, Tania Goncalves, Fabrice Valette, Herman Waldmann, Lucienne Chatenoud, Sylvaine You
Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3(+) regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8(+) T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4(+) T cells in tolerization by CD3 antibodies. We show that both Foxp3(+) Tregs and CD4(+) T cell anergy play a role in the induction of tolerance and its maintenance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#13
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28320914/two-strikes-and-you-re-out-the-pathogenic-interplay-of-coinhibitor-deficiency-and-lymphopenia-induced-proliferation
#14
REVIEW
Kristofor K Ellestad, Colin C Anderson
Lymphopenia-induced proliferation (LIP) occurs when resources for T cell survival in a host are in excess. LIP has been associated with the development of inflammatory disease in situations where an additional disease-predisposing cofactor is present during LIP. This has led to the view of LIP-driven autoimmunity as a two hit model; however, not all cofactors have equal ability to precipitate autoimmunity and we have recently shown that in some circumstances, such as the absence of the coinhibitory molecule PD-1, additional hits are required...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28320090/treatment-with-anti-programmed-cell-death-1-pd-1-antibody-restored-postoperative-cd8-t-cell-dysfunction-by-surgical-stress
#15
Zhirong Sun, Anrong Mao, Yun Wang, Yanjun Zhao, Jiawei Chen, Pingbo Xu, Changhong Miao
Millions of patients benefit from surgery and are exposed to surgical stress. However, ample studies suggest that surgical stress contributes to tumor recurrence or distant metastases. Surgical stress suppresses CD8+ T cells (CTL) function which is vital for eliminating the malignant cells. Anti-programmed cell death 1 (PD-1) therapy is an effective and safe treatment that increases survival rate of patients with multiple cancers, however, whether anti-PD-1 therapy is able to reverse the immunosuppression following surgery remains largely unknown...
March 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28317872/preclinical-evaluation-of-the-efficacy-pharmacokinetics-and-immunogenicity-of-js-001-a-programmed-cell-death-protein-1-pd-1-monoclonal-antibody
#16
Jie Fu, Fang Wang, Li-Hou Dong, Jing Zhang, Cheng-Lian Deng, Xue-Li Wang, Xin-Yao Xie, Jing Zhang, Ruo-Xian Deng, Li-Bo Zhang, Hai Wu, Hui Feng, Bo Chen, Hai-Feng Song
JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails. To date, however, no pre-clinical pharmacological and pharmacokinetic (PK) data are available. In this study, we investigated the efficacy of JS-001 and conducted a preclinical PK study, including the monitoring of anti-drug antibodies (ADAs). We found that JS-001 specifically bound to PD-1 antigen with an EC50 of 21 nmol/L, and competently blocked the binding of PD-1 antigen to PD-L1 and PD-L2 with IC50 of 3...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28315964/biological-predictors-of-radiosensitivity-in-head-and-neck-squamous-cell-carcinoma
#17
Mathias Fiedler, Florian Weber, Matthias G Hautmann, Frank Haubner, Torsten E Reichert, Christoph Klingelhöffer, Stephan Schreml, Johannes K Meier, Arndt Hartmann, Tobias Ettl
OBJECTIVES: The aim of this study is to investigate the influence of prognostic biomarkers on radiosensitivity and survival of advanced head and neck squamous cell carcinomas treated by primary (chemo)radiation. MATERIAL AND METHODS: The clinicopathological data and immunohistochemical staining of p16, c-Met, survivin, PD-1, and PD-L1 of 82 primarily (chemo)irradiated patients with head and neck squamous cell carcinoma were analyzed. Associations with local and locoregional radiation response, overall survival (OS), disease-free (DFS), and disease-specific survival (DSS) were assessed...
March 18, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28315874/multiple-drug-hypersensitivity
#18
Werner J Pichler, Yuttana Srinoulprasert, James Yun, Oliver Hausmann
Multiple drug hypersensitivity (MDH) is a syndrome that develops as a consequence of massive T-cell stimulations and is characterized by long-lasting drug hypersensitivity reactions (DHR) to different drugs. The initial symptoms are mostly severe exanthems or drug rash with eosinophilia and systemic symptoms (DRESS). Subsequent symptoms due to another drug often appear in the following weeks, overlapping with the first DHR, or months to years later after resolution of the initial presentation. The second DHR includes exanthema, erythroderma, DRESS, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hepatitis, and agranulocytosis...
March 18, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28314758/immune-checkpoint-dysfunction-in-medium-and-large-vessel-vasculitis
#19
Ryu Watanabe, Hui Zhang, Gerald Berry, Jorg J Goronzy, Cornelia M Weyand
Giant cell arteritis (GCA) is a granulomatous vasculitis of the aorta and its medium-sized branch vessels. CD4 T-cells, macrophages and dendritic cells build granulomatous infiltrates that injure the vessel wall and elicit a maladaptive response-to-injury. Pathologic consequences include fragmentation of elastic membranes, destruction of the medial layer, microvascular neoangiogenesis, massive outgrowth of myofibroblasts, and lumen-occlusive intimal hyperplasia. Antigens have been suspected to drive the local activation of vasculitogenic CD4 T-cells, but recent data suggest a more generalized defect in the threshold setting of such T-cells, rendering them hyperreactive...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28314688/nivolumab-treatment-for-oesophageal-squamous-cell-carcinoma-an-open-label-multicentre-phase-2-trial
#20
Toshihiro Kudo, Yasuo Hamamoto, Ken Kato, Takashi Ura, Takashi Kojima, Takahiro Tsushima, Shuichi Hironaka, Hiroki Hara, Taroh Satoh, Satoru Iwasa, Kei Muro, Hirofumi Yasui, Keiko Minashi, Kensei Yamaguchi, Atsushi Ohtsu, Yuichiro Doki, Yuko Kitagawa
BACKGROUND: Nivolumab is a human monoclonal IgG4 antibody that inhibits programmed cell death protein 1 (PD-1) expressed on activated T cells. We investigated the safety and activity of nivolumab in patients with treatment-refractory oesophageal cancer. METHODS: We did an open-label, single-arm, multicentre phase 2 study. Eligible patients had advanced squamous-cell carcinoma, adenosquamous-cell carcinoma, or adenocarcinoma of the oesophagus refractory or intolerant to fluoropyrimidine-based, platinum-based, and taxane-based chemotherapy...
March 14, 2017: Lancet Oncology
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