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Programmed cell death ( PD-1 )

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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
#1
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/28442920/a-blockade-of-pd-l1-produced-antitumor-and-antimetastatic-effects-in-an-orthotopic-mouse-pancreatic-cancer-model-via-the-pi3k-akt-mtor-signaling-pathway
#2
Lei Zhao, Cheng Li, Fei Liu, Yonghong Zhao, Jun Liu, Ye Hua, Jinyang Liu, Jiapeng Huang, Chunlin Ge
BACKGROUND: Pancreatic cancer is one of the most aggressive and intractable malignant tumors, and most deaths from pancreatic cancer are related to metastases. It has been demonstrated in vitro that overexpression of programmed death-ligand 1 (PD-L1) correlates with a lack of phosphatase and tensin homologue (PTEN) expression in pancreatic cancer tissue. This loss of PTEN expression may aberrantly activate the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, and thereby promote tumor cell survival, proliferation, and disease progression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28442918/targeting-the-pd-1-pathway-in-pediatric-solid-tumors-and-brain-tumors
#3
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/28441111/phase-ii-study-of-the-efficacy-and-safety-of-pembrolizumab-for-relapsed-refractory-classic-hodgkin-lymphoma
#4
Robert Chen, Pier Luigi Zinzani, Michelle A Fanale, Philippe Armand, Nathalie A Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P Vassilakopoulos, Akihiro Tomita, Bastian von Tresckow, Margaret A Shipp, Yinghua Zhang, Alejandro D Ricart, Arun Balakumaran, Craig H Moskowitz
Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation...
April 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28440953/immunotherapy-with-single-agent-nivolumab-for-advanced-leiomyosarcoma-of-the-uterus-results-of-a-phase-2-study
#5
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
#6
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
#7
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/28438290/programmed-death-ligand-1-pd-l1-expression-and-tumor-microenvironment-implications-for-patients-with-oral-precancerous-lesions
#8
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/28435391/programmed-cell-death-1-checkpoint-inhibitors-in-the-treatment-of-patients-with-advanced-melanoma
#9
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/28435290/altered-status-of-programmed-death-ligand-1-after-recurrence-in-resected-lung-adenocarcinoma-patients
#10
Jun Chen, Hui Li, Ronglin Pang, Jia Huang
PURPOSE: Programmed death-ligand 1 (PD-L1) is found to be overexpressed in non-small cell lung cancer. The present study intended to evaluate the status of PD-L1 expression in patients with resection and recurrent lung adenocarcinoma. PATIENTS AND METHODS: Matched resection and recurrent tumor samples were harvested from 65 lung adenocarcinoma patients. Immunohistochemistry was used to evaluate the status of PD-L1 expression. Kaplan-Meier method was used for survival analysis...
2017: OncoTargets and Therapy
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
#11
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/28432648/rationale-for-new-checkpoint-inhibitor-combinations-in-melanoma-therapy
#12
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/28432616/prognostic-impact-of-pd-1-and-its-ligands-in-renal-cell-carcinoma
#13
REVIEW
Franziska Erlmeier, Wilko Weichert, Andres Jan Schrader, Michael Autenrieth, Arndt Hartmann, Sandra Steffens, Philipp Ivanyi
Programmed death-1 receptor (PD-1) and programmed death-1 receptor-ligand (PD-L1) have been suggested to play a role as prognostic markers in clear cell renal cell carcinoma (ccRCC). The association between PD-L1 and prognosis seems to be more robust than for PD-1. Further, preliminary analyses suggest that neither PD-1 nor its ligands play a role as prognostic markers in non-clear cell RCC, while the prognostic role of PD-L2 in ccRCC as well as in non-clear cell RCC remains unclear.
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28430664/identification-of-a-novel-pd-l1-positive-solid-tumor-transplantable-in-hla-a-0201-drb1-0101-transgenic-mice
#14
Laurie Rangan, Jeanne Galaine, Romain Boidot, Mohamad Hamieh, Magalie Dosset, Julie Francoual, Laurent Beziaud, Jean-René Pallandre, Elodie Lauret Marie Joseph, Afag Asgarova, Christophe Borg, Talal Al Saati, Yann Godet, Jean Baptiste Latouche, Séverine Valmary-Degano, Olivier Adotévi
HLA-A*0201/DRB1*0101 transgenic mice (A2/DR1 mice) have been developed to study the immunogenicity of tumor antigen-derived T cell epitopes. To extend the use and application of this mouse model in the field of antitumor immunotherapy, we described a tumor cell line generated from a naturally occurring tumor in A2/DR1 mouse named SARC-L1. Histological and genes signature analysis supported the sarcoma origin of this cell line. While SARC-L1 tumor cells lack HLA-DRB1*0101 expression, a very low expression of HLA-A*0201 molecules was found on these cells...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430626/expression-of-pd-l1-and-prognosis-in-breast-cancer-a-meta-analysis
#15
Minghui Zhang, Houbin Sun, Shu Zhao, Yan Wang, Haihong Pu, Yan Wang, Qingyuan Zhang
The associations between programmed cell death ligand 1 (PD-L1) and the prognosis of various cancers have always been a research topic of considerable interest. However, the prognostic value of PD-L1 in breast cancer patients remains a controversial subject. We aimed to assess the association between PD-L1 protein expression and clinicopathological features and the impact of this relationship on breast cancer survival. We performed a systematic search of the PubMed, EMBASE, and Cochrane Library databases to determine the correlations among PD-L1 expression, clinicopathological features and overall survival (OS)...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428947/update-on-programmed-death-1-and-programmed-death-ligand-1-inhibition-in-the-treatment-of-advanced-or-metastatic-non-small-cell-lung-cancer
#16
REVIEW
Marco A J Iafolla, Rosalyn A Juergens
PURPOSE: Non-small-cell lung cancer (NSCLC) has a large worldwide prevalence with a high mortality rate. Chemotherapy has offered modest improvements in survival over the past two decades. Immune checkpoint modulation with programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition has shown the promise of changing the future landscape of cancer therapy. This update reviews recent advances in the treatment of NSCLC with immune checkpoint modulation. METHODS: Publications and proceedings were identified from searching PubMed and proceedings from the annual meetings of the American Society of Clinical Oncology, European Society for Medical Oncology, and European Lung Cancer Conference...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28428883/response-after-treatment-with-pembrolizumab-in-a-patient-with-myelophthisis-due-to-melanoma-the-role-of-checkpoint-inhibition-in-the-bone
#17
Samuel Rosner, Filiz Sen, Michael Postow
BACKGROUND: Myelophthisis due to melanoma is a rare phenomenon. Treatment strategies for patients with this serious complication of malignancy have not been well documented, and none have previously reported efficacy of immune checkpoint inhibition. Since bone metastases are not measurable lesions per standard response criteria, the efficacy of immune checkpoint inhibition in the bones is also not well described. CASE PRESENTATION: We describe a patient with widespread melanoma metastases involving the bone marrow causing myelophthisis and pancytopenia who responded to immune checkpoint inhibition with the anti-programmed cell death-1 (PD-1) inhibitor pembrolizumab...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428879/a-systems-biology-approach-to-investigating-the-influence-of-exercise-and-fitness-on-the-composition-of-leukocytes-in-peripheral-blood
#18
Michael P Gustafson, Ara Celi DiCostanzo, Courtney M Wheatley, Chul-Ho Kim, Svetlana Bornschlegl, Dennis A Gastineau, Bruce D Johnson, Allan B Dietz
BACKGROUND: Exercise immunology has become a growing field in the past 20 years, with an emphasis on understanding how different forms of exercise affect immune function. Mechanistic studies are beginning to shed light on how exercise may impair the development of cancer or be used to augment cancer treatment. The beneficial effects of exercise on the immune system may be exploited to improve patient responses to cancer immunotherapy. METHODS: We investigated the effects of acute exercise on the composition of peripheral blood leukocytes over time in a male population of varying fitness...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428785/interferon-gamma-induces-changes-in-natural-killer-nk-cell-ligand-expression-and-alters-nk-cell-mediated-lysis-of-pediatric-cancer-cell-lines
#19
Arianexys Aquino-López, Vladimir V Senyukov, Zlatko Vlasic, Eugenie S Kleinerman, Dean A Lee
Natural killer (NK) cells have therapeutic potential for cancer due to their capacity for targeting tumor cells without prior sensitization. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion that secret 20 times the amount of interferon gamma (IFNγ) than resting NK cells. IFNγ can upregulate major histocompatibility complex (MHC)-class I, an inhibitory ligand for NK cells, but can also upregulate intercellular adhesion molecule 1 (ICAM-1) which promotes NK:target cell interaction for an efficient lysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28427861/divergent-function-of-programmed-death-ligand-1-in-donor-tissue-versus-recipient-immune-system-in-a-murine-model-of-bronchiolitis-obliterans
#20
Katharina Schütte-Nütgen, Olaf Boenisch, Hakima Harrach, Alicia Casey, Indira Guleria, Nader Najafian, Mohamed H Sayegh, Craig J Gerard, Meera Subramaniam
Costimulatory molecules, such as the programmed death ligand (PD-L1), might exert differential effects on T-cell function, depending on the clinical setting and/or immunological environment. Given the impact of T cells on bronchiolitis obliterans (BO) in lung transplantation, we used an established tracheal transplant model inducing BO-like lesions to investigate the impact of PD-L1 on alloimmune responses and histopathological outcome in BO. In contrast to other transplant models in which PD-L1 generally shows protective functions, we demonstrated that PD-L1 has divergent effects depending on its location in donor versus recipient tissue...
April 17, 2017: American Journal of Pathology
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