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PD-1 T cell

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https://www.readbyqxmd.com/read/28449473/anti-pd-1-pd-l1-antibody-versus-conventional-chemotherapy-for-previously-treated-advanced-non-small-cell-lung-cancer-a-meta-analysis-of-randomized-controlled-trials
#1
Yongxun Zhuansun, Fengting Huang, Yumo Du, Lin Lin, Rui Chen, Jianguo Li
BACKGROUND: The anti-PD-1/PD-L1 monoclonal antibody has showed promising results in various cancers via enhancing T cell functions. However, many questions remain in the role and safety in previously-treated, advanced non-small-cell lung cancer (NSCLC). Thus, we conducted a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of anti-PD-1/PD-L1 antibody compared with chemotherapy. METHODS: PubMed, Web of Science and the Cochrane Library database were searched for the studies about the efficacy and safety of anti-PD-1/PD-L1 antibody in previously-treated, progressive NSCLC patients...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28447069/long-term-calorie-restriction-in-humans-is-not-associated-with-indices-of-delayed-immunologic-aging-a-descriptive-study
#2
A Janet Tomiyama, Jeffrey M Milush, Jue Lin, James M Flynn, Pankaj Kapahi, Eric Verdin, Elizabeth Sinclair, Simon Melov, Elissa S Epel
BACKGROUND: Delayed immunologic aging is purported to be a major mechanism through which calorie restriction (CR) exerts its anti-aging effects in non-human species. However, in non-obese humans, the effect of CR on the immune system has been understudied relative to its effects on the cardiometabolic system. OBJECTIVE: To examine whether CR is associated with delayed immunologic aging in non-obese humans. METHODS: We tested whether long-term CR practitioners (average 10.03 years of CR) evidenced decreased expression of T cell immunosenescence markers and longer immune cell telomeres compared to gender-, race/ethnicity-, age-, and education-matched "healthy" Body Mass Index (BMI) and "overweight"/"obese" BMI groups...
March 31, 2017: Nutrition and Healthy Aging
https://www.readbyqxmd.com/read/28446615/proliferation-of-pd-1-cd8-t-cells-in-peripheral-blood-after-pd-1-targeted-therapy-in-lung-cancer-patients
#3
Alice O Kamphorst, Rathi N Pillai, Shu Yang, Tahseen H Nasti, Rama S Akondy, Andreas Wieland, Gabriel L Sica, Ke Yu, Lydia Koenig, Nikita T Patel, Madhusmita Behera, Hong Wu, Megan McCausland, Zhengjia Chen, Chao Zhang, Fadlo R Khuri, Taofeek K Owonikoko, Rafi Ahmed, Suresh S Ramalingam
Exhausted T cells in chronic infections and cancer have sustained expression of the inhibitory receptor programmed cell death 1 (PD-1). Therapies that block the PD-1 pathway have shown promising clinical results in a significant number of advanced-stage cancer patients. Nonetheless, a better understanding of the immunological responses induced by PD-1 blockade in cancer patients is lacking. Identification of predictive biomarkers is a priority in the field, but whether peripheral blood analysis can provide biomarkers to monitor or predict patients' responses to treatment remains to be resolved...
April 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28446566/induction-of-adaptive-immunity-leads-to-nigrostriatal-disease-progression-in-mptp-mouse-model-of-parkinson-s-disease
#4
Goutam Chandra, Avik Roy, Suresh B Rangasamy, Kalipada Pahan
Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is the most widely used animal model for Parkinson's disease (PD), it is known that nigrostriatal pathologies do not persist in the acute MPTP mouse model. This study highlights the importance of adaptive immunity in driving persistent and progressive disease in acute MPTP-intoxicated mice. Although marked infiltration of T cells into the nigra was found on 1 d of MPTP insult, T cell infiltration decreased afterward, becoming normal on 30 d of insult...
April 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28445940/suppression-of-allograft-rejection-by-cd8-cd122-pd-1-tregs-is-dictated-by-their-fas-ligand-initiated-killing-of-effector-t-cells-versus-fas-mediated-own-apoptosis
#5
Huazhen Liu, Yeshu Wang, Qiaohuang Zeng, Yu-Qun Zeng, Chun-Ling Liang, Feifei Qiu, Hong Nie, Zhenhua Dai
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445479/in-vitro-and-in-vivo-antivirus-activity-of-an-anti-programmed-death-ligand-1-pd-l1-rat-bovine-chimeric-antibody-against-bovine-leukemia-virus-infection
#6
Asami Nishimori, Satoru Konnai, Tomohiro Okagawa, Naoya Maekawa, Ryoyo Ikebuchi, Shinya Goto, Yamato Sajiki, Yasuhiko Suzuki, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Shiro Murata, Kazuhiko Ohashi
Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1) in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV) and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow...
2017: PloS One
https://www.readbyqxmd.com/read/28444111/pattern-recognition-receptors-immune-targets-to-enhance-cancer-immunotherapy
#7
T Shekarian, S Valsesia-Wittmann, J Brody, M C Michallet, S Depil, C Caux, A Marabelle
Durable tumor responses and significant levels of disease control rates have been described in more than 20 advanced/metastatic cancer types with B7-family immune checkpoint-targeted anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies. These results and the recent approvals of ipilimumab, pembrolizumab, nivolumab and atezolizumab are currently revolutionizing the way we envision the future of cancer care. However these clinical benefits are not observed in all cancer types and in every patient. Therefore, our clinical challenge is to identify therapeutic strategies which could overcome the primary and secondary resistances to these novel cancer immunotherapies...
April 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28443628/intestinal-microbiota-link-lymphopenia-to-murine-autoimmunity-via-pd-1-cxcr5-dim-b-helper-t-cell-induction
#8
Toshiki Eri, Kimito Kawahata, Takeyuki Kanzaki, Mitsuru Imamura, Kazuya Michishita, Lisa Akahira, Ei Bannai, Noritada Yoshikawa, Yasumasa Kimura, Takeshi Satoh, Satoshi Uematsu, Hirotoshi Tanaka, Kazuhiko Yamamoto
T cell lymphopenia results in peripheral homeostatic expansion to maintain the T cell immune system, which is termed lymphopenia-induced proliferation (LIP). LIP is a potential risk for expanding autoreactive clones to become pathogenic in human and murine autoimmune diseases. However, the ontogeny of T cells that induce autoantibody production by autoreactive B cells in LIP remains unclear. Transfer of CD4(+)CD25(-) conventional T (Tc) cells into T-cell-deficient athymic nude mice has been previously reported as a LIP-induced autoimmune model which develops organ-specific autoimmune diseases and systemic antinuclear antibodies (ANAs)...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442025/protective-effects-of-polydatin-on-experimental-testicular-torsion-and-detorsion-injury-in-rats
#9
Huilian Qiao, He Ma, Wanjun Cao, Hao Chen, Jinhua Wei, Zhen Li
Oxidative stress plays a critical role in the process of testicular torsion and detorsion (T/D). The purpose of the present study was to investigate the protective effect of polydatin (PD) on testicular T/D injury. Rats were randomly divided into three groups, a sham group, a group subjected to 2h torsion followed by 24h detorsion and a group subjected to T/D and injected i.p. with 20mgkg-1 PD 30min before detorsion. Unilateral orchiectomy was performed after 24h of reperfusion. Half the testes were prepared for histological examination by haematoxylin-eosin staining and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) technique...
April 26, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28440484/expression-of-programmed-cell-death1-in-t-follicular-helper-cells-is-regulated-by-prostaglandin-e2-secreted-by-hbv-infected-hepg2-2-1-5-cells
#10
Zhefeng Sui, Ying Shi, Zhiling Gao, Deguang Yang, Zhihao Wang
The present study aimed to investigate the distribution of T follicular helper (Tfh)-cell subsets in patients with hepatitis B virus (HBV) and determine the underlying mechanism of HBV regulation of Tfh cells. The frequency of peripheral blood Tfh subsets was analyzed using flow cytometry. The expression level of programmed cell death‑1 (PD‑1) and prostaglandin E2 (PGE2) was quantified using reverse transcription‑quantitative polymerase chain reaction and western blotting. The PGE2 level in culture supernatant was detected using enzyme‑linked immunosorbent assay...
April 24, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#11
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28435677/control-of-immune-cell-entry-through-the-tumour-vasculature-a-missing-link-in-optimising-melanoma-immunotherapy
#12
REVIEW
Lih Yin Tan, Carmela Martini, Zvi G Fridlender, Claudine S Bonder, Michael P Brown, Lisa M Ebert
Metastatic melanoma remains a fatal disease to many worldwide, even after the breakthrough introduction of targeted therapies such as BRAF inhibitors and immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With advances in our understanding of this disease, as well as the increasing data gathered from patient studies, the significance of the host immune response to cancer progression and response to treatment is becoming clear. More specifically, the presence of intratumoral CD8(+) cytotoxic T-cells correlates with better prognosis whereas the accumulation of monocytes/macrophages and neutrophils in the tumour is often associated with worse prognosis...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28434973/long-term-oral-kinetin-does-not-protect-against-%C3%AE-synuclein-induced-neurodegeneration-in-rodent-models-of-parkinson-s-disease
#13
Adam L Orr, Florentine U Rutaganira, Daniel de Roulet, Eric J Huang, Nicholas T Hertz, Kevan M Shokat, Ken Nakamura
Mutations in the mitochondrial kinase PTEN-induced putative kinase 1 (PINK1) cause Parkinson's disease (PD), likely by disrupting PINK1's kinase activity. Although the mechanism(s) underlying how this loss of activity causes degeneration remains unclear, increasing PINK1 activity may therapeutically benefit some forms of PD. However, we must first learn whether restoring PINK1 function prevents degeneration in patients harboring PINK1 mutations, or whether boosting PINK1 function can offer protection in more common causes of PD...
April 20, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28434648/nivolumab-in-patients-with-advanced-hepatocellular-carcinoma-checkmate-040-an-open-label-non-comparative-phase-1-2-dose-escalation-and-expansion-trial
#14
Anthony B El-Khoueiry, Bruno Sangro, Thomas Yau, Todd S Crocenzi, Masatoshi Kudo, Chiun Hsu, Tae-You Kim, Su-Pin Choo, Jörg Trojan, Theodore H Welling, Tim Meyer, Yoon-Koo Kang, Winnie Yeo, Akhil Chopra, Jeffrey Anderson, Christine Dela Cruz, Lixin Lang, Jaclyn Neely, Hao Tang, Homa B Dastani, Ignacio Melero
BACKGROUND: For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. METHODS: We did a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection...
April 20, 2017: Lancet
https://www.readbyqxmd.com/read/28434400/role-of-modern-immunotherapy-in-gastrointestinal-malignancies-a-review-of-current-clinical-progress
#15
REVIEW
Zin W Myint, Gaurav Goel
Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. There is clearly a significant unmet need for new drugs and therapies to further improve the treatment outcomes of GI malignancies. Immunotherapy is a novel treatment strategy that is emerging as an effective and promising treatment option against several types of cancers. CTLA-4 and PD-1 are critical immune checkpoint molecules that negatively regulate T cell activation via distinct mechanisms...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#16
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28433543/phenformin-inhibits-myeloid-derived-suppressor-cells-and-enhances-the-anti-tumor-activity-of-pd-1-blockade-in-melanoma
#17
Sun Hye Kim, Man Li, Sebastian Trousil, Yaqing Zhang, Marina Pasca di Magliano, Kenneth D Swanson, Bin Zheng
Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated antitumor activity both in vitro and in vivo. However, their potential effects on the tumor microenvironment are largely unknown. Here we report that phenformin selectively inhibits granulocytic myeloid-derived suppressor cells (G-MDSCs) in spleens of tumor bearing mice and ex vivo. Phenformin induces production of reactive oxygen species in G-MDSC, whereas the antioxidant N-acetylcysteine attenuates the inhibitory effects of phenformin...
April 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28432648/rationale-for-new-checkpoint-inhibitor-combinations-in-melanoma-therapy
#18
Mario Mandalà, Carlo Tondini, Barbara Merelli, Daniela Massi
The use of monoclonal antibodies that block immunologic checkpoints, which mediate adaptive immune resistance, has revolutionized the treatment of metastatic melanoma patients. Specifically, targeting single immune suppressive molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or programmed cell death protein 1 (PD-1) expressed on T cells or its primary ligand, programmed cell death ligand 1 (PD-L1), resulted in pronounced clinical benefit for a subset of melanoma patients. Although single-agent immune checkpoint inhibitor therapy has demonstrated promising clinical activity in metastatic melanoma patients, there is still a significant proportion of patients who show primary resistance to these therapies...
April 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28431963/expansion-of-circulating-follicular-t-helper-cells-associates-with-disease-severity-in-childhood-atopic-dermatitis
#19
Krisztina Szabó, Krisztián Gáspár, Zsolt Dajnoki, Gábor Papp, Beáta Fábos, Andrea Szegedi, Margit Zeher
Follicular helper T (TFH) cells play crucial role in B-cell differentiation and antibody production. Although, atopic dermatitis (AD) is often associated with increased serum IgE levels, B-cell mediated responses have not been studied thoroughly. The aim of our study was to investigate the proportion of TFH-like cells in the disease. Twelve children and 17 adults with AD as well as 14 healthy controls were enrolled in the study. The frequency of CD4(+)CXCR5(+)ICOS(+)PD-1(+) TFH-like cells and their IL-21 cytokine production were determined by flow cytometry...
April 18, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28431010/clinical-trial-of-the-anti-pd-l1-antibody-bms-936559-in-hiv-1-infected-participants-on-suppressive-antiretroviral-therapy
#20
Cynthia L Gay, Ronald J Bosch, Justin Ritz, Jason M Hataye, Evgenia Aga, Randall L Tressler, Stephen W Mason, Carey K Hwang, Dennis M Grasela, Neelanjana Ray, Josh C Cyktor, John M Coffin, Edward P Acosta, Richard A Koup, John W Mellors, Joseph J Eron
Background.: Reversing immune exhaustion with an anti-PD-L1 antibody may improve HIV-1-specific immunity and increase clearance of HIV-1 expressing cells. Methods.: Phase I, randomized, double-blind, placebo-controlled dose-escalating study of BMS-936559including HIV-1-infected adults ≥18 to ≤70 years on suppressive antiretroviral therapy with CD4+ counts ≥350 cells/μL and detectable plasma HIV-1 RNA by single copy assay. Data on single infusions of BMS-936559 (0...
April 18, 2017: Journal of Infectious Diseases
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