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PD-1 immune

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https://www.readbyqxmd.com/read/28453847/human-immunodeficiency-virus-persistence-and-t-cell-activation-in-blood-rectal-and-lymph-node-tissue-in-human-immunodeficiency-virus-infected-individuals-receiving-suppressive-antiretroviral-therapy
#1
Gabriela Khoury, Rémi Fromentin, Ajantha Solomon, Wendy Hartogensis, Marisela Killian, Rebecca Hoh, Ma Somsouk, Peter W Hunt, Valerie Girling, Elizabeth Sinclair, Peter Bacchetti, Jenny L Anderson, Frederick M Hecht, Steven G Deeks, Paul U Cameron, Nicolas Chomont, Sharon R Lewin
Background.: Immune activation and inflammation remain elevated in human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) and may contribute to HIV persistence. Methods.: Using flow cytometry expression of CD38, HLA-DR and PD-1 were measured in blood (n = 48), lymph node (LN; n = 9), and rectal tissue (n = 17) from virally suppressed individuals. Total and integrated HIV DNA, 2-LTR circles, and cell-associated unspliced HIV RNA were quantified...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28453554/prognostic-value-of-pd-l1-expression-in-tumor-infiltrating-immune-cells-in-cancers-a-meta-analysis
#2
Tiancheng Zhao, Changfeng Li, Yanhua Wu, Bingjin Li, Bin Zhang
Programmed death-ligand 1 (PD-L1) is a promising target of cancer immune therapy. It not only expressed in tumor cells (TCs) but also up regulated in tumor infiltrating immune cells (TIICs). Although the previous meta-analysis have shown that PD-L1 expression in TCs was a valuable biomarker in predicting cancer prognosis, but few researches systematic evaluated the association between its expression in TIICs and survival of cancer patients. Thus, we performed this meta-analysis to evaluate the prognostic value of PD-L1 expression in TIICs in different types of cancers...
2017: PloS One
https://www.readbyqxmd.com/read/28447277/assessment-of-pd-1-positive-cells-on-initial-and-secondary-resected-tumor-specimens-of-newly-diagnosed-glioblastoma-and-its-implications-on-patient-outcome
#3
Tsubasa Miyazaki, Eiichi Ishikawa, Masahide Matsuda, Hiroyoshi Akutsu, Satoru Osuka, Noriaki Sakamoto, Shingo Takano, Tetsuya Yamamoto, Koji Tsuboi, Akira Matsumura
Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma...
April 26, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28447069/long-term-calorie-restriction-in-humans-is-not-associated-with-indices-of-delayed-immunologic-aging-a-descriptive-study
#4
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/28446566/induction-of-adaptive-immunity-leads-to-nigrostriatal-disease-progression-in-mptp-mouse-model-of-parkinson-s-disease
#5
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/28445951/pd-l1-expression-in-perihilar-and-intrahepatic-cholangiocarcinoma
#6
Jacqueline Fontugne, Jérémy Augustin, Anaïs Pujals, Philippe Compagnon, Benoit Rousseau, Alain Luciani, Christophe Tournigand, Daniel Cherqui, Daniel Azoulay, Jean-Michel Pawlotsky, Julien Calderaro
Cholangiocarcinoma is an aggressive biliary neoplasm lacking effective therapeutic agents. Immunotherapies targeting the PD-L1/PD-1 immune checkpoint have shown encouraging results in solid and hematologic cancers in clinical trials. Response to these immunomodulators is correlated with PD-L1 expression. Our goal was to characterize PD-L1 expression in intra-hepatic (iCCA) and perihilar (pCCA) cholangiocarcinomas, and to correlate our results with clinicopathological features, density of tumor-infiltrating lymphocytes (TILs) and PD-1 expression...
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
#7
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
#8
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
#9
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/28442918/targeting-the-pd-1-pathway-in-pediatric-solid-tumors-and-brain-tumors
#10
REVIEW
Lars M Wagner, Val R Adams
While remarkable advances have been made in the treatment of pediatric leukemia over the past decades, new therapies are needed for children with advanced solid tumors and high-grade brain tumors who fail standard chemotherapy regimens. Immunotherapy with immune checkpoint inhibitors acting through the programmed cell death-1 (PD-1) pathway has shown efficacy in some chemotherapy-resistant adult cancers, generating interest that these agents may also be helpful to treat certain refractory pediatric malignancies...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28442891/spotlight-on-nivolumab-in-the-treatment-of-renal-cell-carcinoma-design-development-and-place-in-therapy
#11
REVIEW
Vyshak Alva Venur, Monika Joshi, Kenneth G Nepple, Yousef Zakharia
Several tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors and molecules inhibiting the mammalian target of rapamycin are being used for management of metastatic renal cell carcinoma (mRCC); however, there is still a potential for improvement. Immune checkpoint inhibitors like nivolumab and other PD-1/PD-L1 inhibitors provide an alternative approach for patients with mRCC. In this article, the authors review the safety profile and outcomes of phase 1, 2, and 3 clinical trials of nivolumab in mRCC...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28440953/immunotherapy-with-single-agent-nivolumab-for-advanced-leiomyosarcoma-of-the-uterus-results-of-a-phase-2-study
#12
Eytan Ben-Ami, Constance M Barysauskas, Sarah Solomon, Kadija Tahlil, Rita Malley, Melissa Hohos, Kathleen Polson, Margaret Loucks, Mariano Severgnini, Tara Patel, Amy Cunningham, Scott J Rodig, F Stephen Hodi, Jeffrey A Morgan, Priscilla Merriam, Andrew J Wagner, Geoffrey Shapiro, Suzanne George
BACKGROUND: Immunotherapy has changed the therapeutic landscape in oncology. Advanced uterine leiomyosarcoma (ULMS) remains an incurable disease in most cases, and despite new drug approvals, improvements in overall survival have been modest at best. The goal of this study was to evaluate programmed-death 1 (PD-1) inhibition with nivolumab in this patient population. METHODS: This single-center phase 2 trial completed enrollment between May and October 2015. Patients received 3 mg/kg of intravenous nivolumab on day 1 of each 2-week cycle until disease progression or unacceptable toxicity...
April 25, 2017: Cancer
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
#13
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/28439919/motor-polyradiculopathy-during-pembrolizumab-treatment-of-metastatic-melanoma
#14
Maria Sepúlveda, Eugenia Martinez-Hernandez, Lydia Gaba, Ivan Victoria, Nuria Sola-Valls, Neus Falgàs, Jordi Casanova-Molla, Francesc Graus
INTRODUCTION: Pembrolizumab, a monoclonal antibody directed against the immune checkpoint PD-1 (programmed cell death-1 receptor), has improved survival in patients with advanced melanoma. Neuromuscular immune-mediated side effects have been rarely reported. METHODS: We describe a 44-year-old man with metastatic melanoma who presented with progressive muscle weakness after 23 doses of pembrolizumab. RESULTS: The patient developed asymmetric, proximal muscle weakness and atrophy in all four limbs...
April 25, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28438383/remitting-seronegative-symmetrical-synovitis-with-pitting-edema-rs3pe-syndrome-induced-by-nivolumab
#15
Marie-Léa Gauci, Barouyr Baroudjian, Pauline Laly, Isabelle Madelaine, Laetitia Da Meda, Laetitia Vercellino, Martine Bagot, Frédéric Lioté, Cécile Pages, Céleste Lebbé
INTRODUCTION: A new articular syndrome described as immunrelated side effect of immunotherapy: PD-1 inhibitors have revolutionized the treatment of advanced melanoma but are responsible for immune-related toxicity. We report a case of remitting seronegative symetrical synovitis with pitting edema (RS3PE) syndrome induced by nivolumab. CASE REPORT: A 80 year-old man with stage IV BRAF-wild type and NRAS exon 2-mutated melanoma was treated first line by nivolumab 3mg/kg every 2 weeks...
March 8, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28438290/programmed-death-ligand-1-pd-l1-expression-and-tumor-microenvironment-implications-for-patients-with-oral-precancerous-lesions
#16
Takahiro Yagyuu, Kinta Hatakeyama, Mitsuhiko Imada, Miyako Kurihara, Yumiko Matsusue, Kazuhiko Yamamoto, Chiho Obayashi, Tadaaki Kirita
OBJECTIVES: Cancer immunoediting represents a relatively novel concept attempting to explain the process of tumor escape from the host immune system response. Here, we attempted to elucidate the role of programmed death ligand 1 (PD-L1), the tumor microenvironment, and tumor escape mechanisms that allow malignant transformation of oral precancerous lesions. MATERIALS AND METHODS: Patients with oral precancerous lesions managed at the Nara Medical University Hospital, Japan, (n=120) were enrolled in this study...
May 2017: Oral Oncology
https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#17
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
#18
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/28435391/programmed-cell-death-1-checkpoint-inhibitors-in-the-treatment-of-patients-with-advanced-melanoma
#19
REVIEW
Jacek Mackiewicz, Andrzej Mackiewicz
The treatment landscape of advanced melanoma has changed significantly following the discovery and marketing authorisation of immune checkpoints inhibitors. Ipilimumab (anti-CTLA-4) was the first one to be approved, and it. demonstrated long-term survival in about 20% of patients. Subsequently, anti-programmed cell death-1 (a-PD-1) antibodies (pembrolizuamb, nivolumab), inhibitors of PD-1/programmed cell death-1 ligand (PD1-L) synapse, showed higher clinical efficacy with lower toxicity comparing to ipilimumab...
2017: Contemporary Oncology Współczesna Onkologia
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
#20
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
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