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https://www.readbyqxmd.com/read/29341118/inhibition-of-the-fgl2-fc%C3%AE-riib-riii-immunosuppressive-pathway-enhances-antiviral-t-cell-and-b-cell-responses-leading-to-clearance-of-lcmv-cl-13
#1
Olga Klingberg, Ramzi Khattar, Kaveh Farrokhi, Dario Ferri, Nataliya Yavorska, Jianhua Zhang, Hassan Sadozai, Oyedele Adeyi, Andrzej Chruscinski, Gary A Levy, Nazia Selzner
Persistent viruses evade immune detection by interfering with virus-specific innate and adaptive antiviral immune responses. Fibrinogen-Like Protein-2 (FGL2) is a potent effector molecule of CD4+ CD25+ FoxP3+ regulatory T cells (Treg) and exerts its immunosuppressive activity following ligation to its cognate receptor, FcγRIIB/RIII. The role of FGL2 in the pathogenesis of chronic viral infection caused by Lymphocytic Choriomeningitis Virus Clone-13 (LCMV cl-13) was assessed in this study. Chronically infected fgl2+/+ mice had increased plasma levels of FGL2, with reduced expression of the maturation markers, CD80, CD86 and MHC-II on macrophages and dendritic cells (DC) and impaired production of neutralizing antibody...
January 17, 2018: Immunology
https://www.readbyqxmd.com/read/29340396/synthesis-and-antiproliferative-activity-of-a-series-of-new-platinum-and-palladium-diphosphane-complexes
#2
Carleen Cullinane, Glen B Deacon, Penny R Drago, Anja P Erven, Peter C Junk, Jenny Luu, Gerd Meyer, Simon Schmitz, Ingo Ott, Julia Schur, Lorraine K Webster, Axel Klein
New organometallic complexes [M(dppe)(R)2] {where M = Pt or Pd, dppe = 1,2-bis(diphenylphosphano)ethane, and R = C6F4H-x (x = 6,5,4), C6F3H2-3,5, C6F3H2-5,6, C6F3H2-3,6, C6F4(OMe)-4, and C6F4(cyclo-C5H10N)-4, the numbers x refer to the positions of the protons in the polyfluoroaryl ligands} were synthesised either through transmetalation from the dichlorido complexes [M(dppe)Cl2] or through ligand exchange using [M(diene)Cl2] precursor complexes with diene = 1,5-cyclooctadiene (cod) or 1,5-hexadiene (hex). Alternatively, [M(dppX)Cl(R)] complexes with dppX = dppm (1,1-bis(diphenylphosphano)methane), dppe, dppp (1,3-bis(diphenylphosphano)propane), and dppb (1,4-bis(diphenylphosphano)butane) were prepared in decarboxylation reactions from thallium(i) carboxylates Tl(O2CR)...
January 17, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29340095/tumoral-immune-infiltrate-if-pd-l1-expression-and-role-of-cd8-tia-1-lymphocytes-in-localized-osteosarcoma-patients-treated-within-protocol-isg-os1
#3
Emanuela Palmerini, Claudio Agostinelli, Piero Picci, Stefano Pileri, Teresa Marafioti, Pier-Luigi Lollini, Katia Scotlandi, Alessandra Longhi, Maria Serena Benassi, Stefano Ferrari
Background: We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. Methods: 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338562/targeted-microbubbles-with-ultrasound-irradiation-and-pd-1-inhibitor-to-increase-antitumor-activity-in-b-cell-lymphoma
#4
Shiya Zheng, Dan Song, Xiaoxiao Jin, Haijun Zhang, Mohanad Aldarouish, Yan Chen, Cailian Wang
AIM: Severe cardiac toxicity of doxorubicin and an immunosuppressive tumor micro-environment become main obstacles for the effective treatment of B-cell lymphoma. In this research, rituximab-conjugated and doxorubicin-loaded microbubbles (RDMs) were designed for exploring a combination approach of targeted microbubbles with ultrasound (US) irradiation and PD-1 inhibitor to overcome obstacles mentioned above. METHODS: In vivo studies were performed on SU-DHL-4 cell-grafted mice and ex vivo studies were performed on CD20+ human SU-DHL-4 cells and human T cells...
January 17, 2018: Nanomedicine
https://www.readbyqxmd.com/read/29337640/molecular-determinants-of-response-to-anti-programmed-cell-death-pd-1-and-anti-programmed-death-ligand-pd-l-ligand-1-blockade-in-patients-with-non-small-cell-lung-cancer-profiled-with-targeted-next-generation-sequencing
#5
Hira Rizvi, Francisco Sanchez-Vega, Konnor La, Walid Chatila, Philip Jonsson, Darragh Halpenny, Andrew Plodkowski, Niamh Long, Jennifer L Sauter, Natasha Rekhtman, Travis Hollmann, Kurt A Schalper, Justin F Gainor, Ronglai Shen, Ai Ni, Kathryn C Arbour, Taha Merghoub, Jedd Wolchok, Alexandra Snyder, Jamie E Chaft, Mark G Kris, Charles M Rudin, Nicholas D Socci, Michael F Berger, Barry S Taylor, Ahmet Zehir, David B Solit, Maria E Arcila, Marc Ladanyi, Gregory J Riely, Nikolaus Schultz, Matthew D Hellmann
Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically available tools to optimize use of ICIs and understand the molecular determinants of response are needed. Targeted next-generation sequencing (NGS) is increasingly routine, but its role in identifying predictors of response to ICIs is not known. Methods Detailed clinical annotation and response data were collected for patients with advanced non-small-cell lung cancer treated with anti-programmed death-1 or anti-programmed death-ligand 1 [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK-IMPACT; n = 240)...
January 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29333023/nivolumab-pearls-of-evidence
#6
REVIEW
Pratishtha B Chaudhari
Purpose: Nivolumab is one of the most extensively studied immune checkpoint inhibitors across various tumor types. In this narrative review, the current clinical efficacy and safety data of anti-programmed death-1 (PD-1) nivolumab for nonsmall cell lung cancer (NSCLC) and renal cell cancer (RCC) are elucidated. Methods: Systematic search was done on Pubmed, Medline, Embase, Web of Knowledge, and Cochrane Central through September 2016 for controlled prospective interventional studies of nivolumab across two indications - NSCLC and RCC...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29330552/dosimetry-prediction-for-clinical-translation-of-64cu-pembrolizumab-immunopet-targeting-human-pd-1-expression
#7
Arutselvan Natarajan, Chirag B Patel, Frezghi Habte, Sanjiv S Gambhir
The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29326088/age-effects-of-distinct-immune-checkpoint-blockade-treatments-in-a-mouse-melanoma-model
#8
Álvaro Padrón, Vincent Hurez, Harshita B Gupta, Curtis A Clark, Sri Lakshmi Pandeswara, Bin Yuan, Robert S Svatek, Mary Jo Turk, Justin M Drerup, Rong Li, Tyler J Curiel
Cancer immunotherapy has shown remarkable recent progress. Immune checkpoint blocking antibodies have become the most successful anti-cancer agent class ever developed, with six distinct agents approved since 2011 for a wide variety of cancers. Although age is the biggest risk factor for cancer (aside from selected early-onset pediatric cancers), these agents were tested pre-clinically in young hosts, and there is remarkably little published on the effects of host age on treatment outcomes in pre-clinical studies or human clinical trials...
January 8, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29325739/anti-programmed-cell-death-1-ligand-1-pd-1-pd-l1-antibodies-for-the-treatment-of-urothelial-carcinoma-state-of-the-art-and-future-development
#9
REVIEW
Thomas Powles, Andrea Necchi, Galit Rosen, Subramanian Hariharan, Andrea B Apolo
Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint inhibitors has expanded a previously limited pool of effective treatment options for patients with metastatic urothelial carcinoma, particularly those with recurring or refractory disease and those who are ineligible for cisplatin. This review reports key findings from completed and ongoing clinical trials that highlight the potential of PD-1/PD-L1 blockade in urothelial carcinoma. A literature search was performed of PubMed, Embase, ClinicalTrials...
December 6, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29320474/high-response-rate-to-pd-1-blockade-in-desmoplastic-melanomas
#10
Zeynep Eroglu, Jesse M Zaretsky, Siwen Hu-Lieskovan, Dae Won Kim, Alain Algazi, Douglas B Johnson, Elizabeth Liniker, Ben Kong, Rodrigo Munhoz, Suthee Rapisuwon, Pier Federico Gherardini, Bartosz Chmielowski, Xiaoyan Wang, I Peter Shintaku, Cody Wei, Jeffrey A Sosman, Richard W Joseph, Michael A Postow, Matteo S Carlino, Wen-Jen Hwu, Richard A Scolyer, Jane Messina, Alistair J Cochran, Georgina V Long, Antoni Ribas
Desmoplastic melanoma is a rare subtype of melanoma characterized by dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations, and is highly associated with ultraviolet light-induced DNA damage. We analysed sixty patients with advanced desmoplastic melanoma who had been treated with antibodies to block programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1). Objective tumour responses were observed in forty-two of the sixty patients (70%; 95% confidence interval 57-81%), including nineteen patients (32%) with a complete response...
January 10, 2018: Nature
https://www.readbyqxmd.com/read/29317815/double-stranded-phosphodiester-cytosine-guanine-oligodeoxynucleotide-complexed-with-calcium-phosphate-as-a-potent-vaccine-adjuvant-for-activating-cellular-and-th1-type-humoral-immunities
#11
Nobutaka Hanagata, Xianglan Li, Min-Hua Chen, Jie Li, Shinya Hattori
Conventional class B cytosine-guanine (CpG) (CpG-B) oligodeoxynucleotide (ODNs) consisting of a single-stranded (ss) phosphorothioate (PT) backbone (ss CpG-B-PT) is converted from a proinflammatory cytokine inducer to a type-I interferon (IFN) inducer when complexed with cationic materials. In this study, we designed ss CpG-B and double-stranded (ds) CpG-B ODNs with a phosphodiester (PD) backbone (ss CpG-B-PD and ds CpG-B-PD, respectively) that became type-I IFN inducers upon complexation with Lipofectamine 2000 (Lipo), a cationic liposome...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29315581/parkinson-disease-related-dj-1-modulates-the-expression-of-uncoupling-protein-4-against-oxidative-stress
#12
Shaoqing Xu, Xiaodong Yang, Yiwei Qian, Qin Xiao
Loss of function mutations of DJ-1 (PARK7) have been linked to the pathogenesis of Parkinson disease (PD). Antioxidative stress is one of the multi-protective functions of DJ-1, and oxidation of cysteine 106 (Cys106) has been proposed to regulate the protective activity of DJ-1. Uncoupling protein 4 (UCP4) is located in the inner membrane of mitochondria and functions to protect against oxidative stress. In this study, we used neuronal (SH-SY5Y) cells and DJ-1 knockout (KO) mice to elucidate whether DJ-1 regulated oxidative stress via modulating the expression of UCP4, and the underlying mechanism...
January 8, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29303606/potential-neuroprotective-and-anti-apoptotic-properties-of-a-long-lasting-stable-analog-of-ghrelin-an-in-vitro-study-using-sh-sy5y-cells
#13
A Popelová, A Kákonová, L Hrubá, J Kuneš, L Maletínská, B Železná
Neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are increasing in prevalence. Currently, there are no effective and specific treatments for these disorders. Recently, positive effects of the orexigenic hormone ghrelin on memory and learning were demonstrated in mouse models of AD and PD. In this study, we tested the potential neuroprotective properties of a stable and long-lasting ghrelin analog, Dpr(3)ghrelin (Dpr(3)ghr), in SH-SY5Y neuroblastoma cells stressed with 1...
January 5, 2018: Physiological Research
https://www.readbyqxmd.com/read/29299180/regulation-of-pd-1-pd-l1-pathway-and-resistance-to-pd-1-pd-l1-blockade
#14
REVIEW
Jie Bai, Zhitao Gao, Xiang Li, Liang Dong, Weidong Han, Jing Nie
Immune checkpoint blockades, such as inhibitors against programmed death 1 (PD-1) and its ligand (PD-L1), have received extensive attention in the past decade because of their dramatic clinical outcomes in advanced malignancies. However, both primary and acquired resistance becomes one of the major obstacles, which greatly limits the long-lasting effects and wide application of PD-1/PD-L1 blockade therapy. PD-1/PD-L1 both regulates and is regulated by cellular signaling pathways and epigenetic modification, thus inhibiting the proliferation and effector function of T and B cells...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296917/checkpoint-blockade-in-hodgkin-and-non-hodgkin-lymphoma
#15
REVIEW
Reid W Merryman, Philippe Armand, Kyle T Wright, Scott J Rodig
Classical Hodgkin lymphoma (cHL) is characterized by nearly universal genetic alterations in 9p24.1, resulting in constitutive expression of PD-1 ligands. This likely underlies the unique sensitivity of cHL to PD-1 blockade, with response rates of ∼70% in relapsed/refractory disease. There are now numerous clinical trials testing PD-1 inhibitors in earlier stages of treatment and in combination with many other therapies. In general, non-Hodgkin lymphomas (NHLs) do not display a high frequency of 9p24.1 alterations and do not share cHL's vulnerability to PD-1 blockade...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296862/brafv600e-accelerates-disease-progression-and-enhances-immune-suppression-in-a-mouse-model-of-b-cell-leukemia
#16
Yo-Ting Tsai, Aparna Lakshmanan, Amy Lehman, Bonnie K Harrington, Fabienne McClanahan Lucas, Minh Tran, Ellen J Sass, Meixiao Long, Alan D Flechtner, Florinda Jaynes, Krista La Perle, Vincenzo Coppola, Gerard Lozanski, Natarajan Muthusamy, John C Byrd, Michael R Grever, David M Lucas
Mutated mitogen-activated protein kinase (MAPK) pathway components promote tumor survival, proliferation, and immune evasion in solid tumors. MAPK mutations occur in hematologic cancers as well, but their role is less clear and few models are available to study this. We developed an in vivo model of disseminated BRAFV600E B-cell leukemia to determine the effects of this mutation on tumor development and immune evasion. Mice with B-cell-restricted BRAFV600E expression crossed with the Eµ-TCL1 model of chronic lymphocytic leukemia (CLL) developed leukemia significantly earlier (median, 4...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296784/high-proportions-of-pd-1-and-pd-l1-leukocytes-in-classical-hodgkin-lymphoma-microenvironment-are-associated-with-inferior-outcome
#17
Peter Hollander, Peter Kamper, Karin Ekstrom Smedby, Gunilla Enblad, Maja Ludvigsen, Julie Mortensen, Rose-Marie Amini, Stephen Hamilton-Dutoit, Francesco d'Amore, Daniel Molin, Ingrid Glimelius
Immune checkpoint inhibition targeting the programmed death receptor (PD)-1 pathway is a novel treatment approach in relapsed and refractory classical Hodgkin lymphoma (cHL). Identifying patients with a high risk of treatment failure could support the use of PD-1 inhibitors as front-line treatment. Our aim was to investigate the prognostic impact of PD-1, programmed death-ligand 1 (PD-L1), and PD-L2 in the tumor microenvironment in diagnostic biopsies of patients with cHL. Patients from Denmark and Sweden, diagnosed between 1990 and 2007 and ages 15 to 86 years, were included...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296194/changes-in-pd-l1-expression-according-to-tumor-infiltrating-lymphocytes-of-acquired-egfr-tki-resistant-egfr-mutant-non-small-cell-lung-cancer
#18
Tae-Jung Kim, Soon Auck Hong, Okran Kim, Seung Joon Kim, Ji-Hyun Yang, Eun Kyo Joung, Jin-Hyoung Kang, Sook-Hee Hong
Backgrounds: EGFR-mutant non-small cell lung cancer (NSCLC) that developed acquired resistance to EGFR-tyrosine kinase (TKI) are potential candidates for programmed death 1 (PD1) inhibitor. Results: TPS≥1% for PD-L1 and low CD8 + TIL in post-TKI tumor showed a trend for a lower PFS of EGFR-TKIs (14.2 vs 9.9 months; P = 0.060) (cohort A). Only 2 of 22 specimens (9.1%) with an acquired EGFR exon 20 T790M mutation exhibited in post-TKI TPS≥50% for PD-L1. The degree in post-TKI tumor of PD-L1 expression was varied in 19 patients (40...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29289977/anti-pd-1-induced-high-grade-hepatitis-associated-with-corticosteroid-resistant-t-cells-a-case-report
#19
Helen M McGuire, Elena Shklovskaya, Jarem Edwards, Paul R Trevillian, Geoffrey W McCaughan, Patrick Bertolino, Catriona McKenzie, Ralph Gourlay, Stuart J Gallagher, Barbara Fazekas de St Groth, Peter Hersey
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control...
December 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29288900/increased-pd-1-cd154-tfh-cells-are-possibly-the-most-important-functional-subset-of-pd-1-t-follicular-helper-cells-in-adult-patients-with-minimal-change-disease
#20
Tao Li, Yunpeng Shi, Weixia Sun, Haifeng Wang, Quan Wang, Yanfang Jiang
T follicular helper (Tfh) cells, especially programmed cell death protein 1 (PD-1)+ Tfh cells, exert important functions in the normal immune response. The purpose of this study was to determine the frequency of different subsets of PD-1+ Tfh cells and their functional effects in adult patients with minimal change disease (MCD). The frequencies of circulating PD-1+, PD-1+CD154+, and PD-1+interleukin (IL)-21+ Tfh cells, and CD38+CD19+ and CD38+CD19+CD40+ B cells, as well as serum IL-2, IL-4, IL-17A, IL-6, IL-21, and interferon (IFN)-γ were significantly increased in the MCD patients compared with the healthy controls (HCs) (P < 0...
December 27, 2017: Molecular Immunology
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