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https://www.readbyqxmd.com/read/28644134/the-conundrum-of-the-epstein-barr-virus-associated-gastric-carcinoma-in-the-americas
#1
REVIEW
Gonzalo Carrasco-Avino, Ismael Riquelme, Oslando Padilla, Miguel Villaseca, Francisco R Aguayo, Alejandro H Corvalan
Epstein-Barr virus-associated gastric carcinoma shows a higher prevalence in the Americas than Asia. We summarize all studies of Epstein Barr virus-associated gastric carcinoma in the Americas, focusing on host characteristics, environmental associations and phylogeographic diversity of Epstein-Barr virus strains. In the Americas, the prevalence of Epstein Barr virus-associated gastric carcinoma is 11.4%, more frequent in males and portray predominantly diffuse-type histology. EBERs, EBNAs, BARTs and LMP are the highest expressed genes; their variations in healthy individuals may explain the phylogeographic diversity of Epstein-Barr virus across the region...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#2
Johan Mj Van den Bergh, Evelien Ljm Smits, Zwi N Berneman, Tim Ja Hutten, Hans De Reu, Viggo Fi Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DCs) is an appealing strategy to boost the GVT-response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28621910/allospecific-memory-b-cell-responses-are-dependent-on-autophagy
#3
Miguel Fribourg, Jie Ni, F Nina Papavasiliou, Zhenyu Yue, Peter S Heeger, Jeremy S Leventhal
Long-lived, donor-reactive memory B cells (Bmem) can produce alloantibodies that mediate transplant injury. Autophagy, an intrinsic mechanism of cell organelle/component recycling, is required for Bmem survival in infectious and model antigen systems but whether autophagy impacts alloreactive Bmem is unknown. We studied mice with an inducible yellow fluorescent protein (YFP) reporter expressed under the Activation-Induced Cytidine Deaminase (AID) promoter active in B cells undergoing germinal center reactions...
June 16, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28619999/pd-l2-expression-in-human-tumors-relevance-to-anti-pd-1-therapy-in-cancer
#4
Jennifer H Yearley, Christopher Gibson, Ni Yu, Christina Moon, Erin Murphy, Jonathan Juco, Jared Lunceford, Jonathan Cheng, Laura Q M Chow, Tanguy Y Seiwert, Masahisa Handa, Joanne E Tomassini, Terrill McClanahan
Purpose: Tumor-associated PD-L1 expression is predictive of clinical response to PD-1-directed immunotherapy. However, PD-L1-negative patients may also respond to PD-1 checkpoint blockade, suggesting that other PD-1 ligands may be relevant to the clinical activity of these therapies. The prevalence of PD-L2, the other known ligand of PD-1, and its relationship to response to anti-PD-1 therapy were evaluated.Experimental Design: PD-L2 expression was assessed in archival tumor tissue from seven indications using a novel immunohistochemical assay...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28615524/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#5
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611041/an-immunosuppressive-dendritic-cell-subset-accumulates-at-secondary-sites-and-promotes-metastasis-in-pancreatic-cancer
#6
Justin A Kenkel, William W Tseng, Matthew G Davidson, Lorna Tolentino, Okmi Choi, Nupur Bhattacharya, E Scott Seeley, Daniel Winer, Nathan E Reticker-Flynn, Edgar G Engleman
Pancreatic ductal adenocarcinoma (PDAC) after complete surgical resection is often followed by distant metastatic relapse for reasons that remain unclear. In this study, we investigated how the immune response at secondary sites affects tumor spread in murine models of metastatic PDAC. Early metastases were associated with dense networks of CD11b(+)CD11c(+)MHC-II(+)CD24(+)CD64(low)F4/80(low) dendritic cells (DC), which developed from monocytes in response to tumor-released GM-CSF. These cells uniquely expressed MGL2 and PD-L2 in the metastatic microenvironment and preferentially induced the expansion of T regulatory cells (Treg) in vitro and in vivo...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28588322/a-phase-ib-study-of-pembrolizumab-plus-chemotherapy-in-patients-with-advanced-cancer-pembroplus
#7
Glen J Weiss, Jordan Waypa, Lisa Blaydorn, Jessica Coats, Kayla McGahey, Ashish Sangal, Jiaxin Niu, Cynthia A Lynch, John H Farley, Vivek Khemka
BACKGROUND: Pembrolizumab (P) is an anti-PD-1 antibody that blocks the interaction between programmed cell death protein 1 (PD-1) on T-cells and PD-L1 and PD-L2 on tumour cells. A phase Ib trial of P plus chemotherapy was undertaken to evaluate the safety and efficacy. METHODS: Patients with advanced, metastatic solid tumours were enrolled onto one of six treatment arms. Pembrolizumab was given: with gemcitabine (G), G+docetaxel (D), G+nab-paclitaxel (NP), G+vinorelbine (V) or irinotecan (I) until progression or toxicity, or with liposomal doxorubicin (LD) for up to 15 cycles, progression or toxicity...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28575876/hdac-inhibitors-enhance-the-immunotherapy-response-of-melanoma-cells
#8
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Paul Dent
We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the immunogenic protein HMGB1 into the extracellular environment. Very similar data were obtained in ovarian and H&NSCC PDX isolates, and in established tumor cell lines from the lung and kidney...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28570665/pd-l1-pd-l2-expressing-b-1-cells-inhibit-alloreactive-t-cells-in-mice
#9
Takayuki Hirose, Yuka Tanaka, Asuka Tanaka, Hiroshi Sakai, Yu Sasaki, Nobuo Shinohara, Hideki Ohdan
B cells constitute a complex system of antigen-presenting cells (APCs) and exist as distinct subsets that differ in their lineage affiliation, surface molecule expression, and biological function, thus potentially regulating the immune response. In this study, we investigated the immune-regulatory roles of murine B cell subsets as regulatory APCs targeting alloreactive T cells. Either splenic B cells, peritoneal cavity (PerC) B cells, or non-B cells from Balb/c mice were intravenously injected into B6 mice...
2017: PloS One
https://www.readbyqxmd.com/read/28561677/immunotherapy-for-esophageal-and-gastric-cancer
#10
Ronan J Kelly
PD-L1 upregulation occurs in approximately 40% of gastroesophageal cancers. However, unlike other solid tumors, there is minimal PD-L1 expressed on the cancer cells; rather, expression occurs predominantly on infiltrating myeloid cells. Preliminary clinical data involving single-agent PD-1/PD-L1 inhibitors in metastatic gastroesophageal cancer have reported response rates of 22%-27% for patients with PD-L1(+) tumors and 10%-17% for unselected patients. The phase III ONO-4538-12 (ATTRACTION 2) trial has demonstrated an improved overall survival for nivolumab compared with placebo for patients with heavily pretreated gastric cancer...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28556548/soluble-form-of-pd-1-and-pd-l2-contributes-to-disease-severity-and-progression-in-systemic-sclerosis
#11
Takemichi Fukasawa, Ayumi Yoshizaki, Satoshi Ebata, Kouki Nakamura, Ryosuke Saigusa, Syunsuke Miura, Takashi Yamashita, Megumi Hirabayashi, Yohei Ichimura, Takashi Taniguchi, Yoshihide Asano, Hisashi Shimizu, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Shinichi Sato
OBJECTIVE: To determine the function and serum levels of soluble forms of programmed death-1 (sPD-1) and its ligand of PD-L2 (sPD-L2) in patients with systemic sclerosis (SSc). METHODS: The serum levels of sPD-1 and sPD-L2 levels in 91 patients with SSc were examined by enzyme-linked immunosorbent assay (ELISA). The expression of PD-1 and PD-L2 on T cells, B cells, and macrophages was quantified by flow cytometry analysis. The effects of PD-1 and PD-L2 blocking were also analyzed by micro-ELISA which can measure the very low amount of cytokines...
May 26, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28552844/pd-l1-a-novel-prognostic-biomarker-in-head-and-neck-squamous-cell-carcinoma
#12
Tim Müller, Martin Braun, Dimo Dietrich, Seher Aktekin, Simon Höft, Glen Kristiansen, Friederike Göke, Andreas Schröck, Johannes Brägelmann, Stefanie A E Held, Friedrich Bootz, Peter Brossart
BACKGROUND: The PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28552541/primary-central-nervous-system-diffuse-large-b-cell-lymphoma-shows-an-activated-b-cell-like-phenotype-with-co-expression-of-c-myc-bcl-2-and-bcl-6
#13
Xiaomei Li, Ying Huang, Chengfeng Bi, Ji Yuan, Hong He, Hong Zhang, QiuBo Yu, Kai Fu, Dan Li
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, whose main prognostic factor is closely related to germinal center B-cell-like subtype (GCB- DLBCL) or activated B-cell-like type (non-GCB-DLBCL). The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear. This study aims to stratify primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) according to the cell-of-origin (COO) and to investigate the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53, further to elucidate the reason why primary central nervous system diffuse large B-cell lymphoma possesses a poor clinical outcome as well...
June 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28546465/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#14
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
May 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28539588/cooperation-of-oncolytic-herpes-virotherapy-and-pd-1-blockade-in-murine-rhabdomyosarcoma-models
#15
Chun-Yu Chen, Pin-Yi Wang, Brian Hutzen, Les Sprague, Hayley M Swain, Julia K Love, Joseph R Stanek, Louis Boon, Joe Conner, Timothy P Cripe
Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#16
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537531/clinical-features-of-nivolumab-induced-thyroiditis-a-case-series-study
#17
Ichiro Yamauchi, Yoriko Sakane, Yorihide Fukuda, Toshihito Fujii, Daisuke Taura, Masakazu Hirata, Keisho Hirota, Yohei Ueda, Yugo Kanai, Yui Yamashita, Eri Kondo, Masakatsu Sone, Akihiro Yasoda, Nobuya Inagaki
BACKGROUND: The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. It consists of the PD-1 receptor and its two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Nivolumab is an anti-PD-1 monoclonal antibody approved for malignant melanoma, advanced non-small cell lung cancer, and advanced renal cell carcinoma in Japan. Thyrotoxicosis and hypothyroidism have both been reported in international Phase 3 studies and national post-marketing surveillance of nivolumab in Japan...
June 21, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28521800/immunogenicity-and-immunomodulatory-effects-of-the-human-chondrocytes-hchonj
#18
Chae-Lyul Lim, Yeon-Ju Lee, Jong-Ho Cho, Heonsik Choi, Bumsup Lee, Myung Chul Lee, Sujeong Kim
BACKGROUND: Invossa™ (TissueGene-C) is a cell and gene therapy for osteoarthritis. It is composed of primary human chondrocytes (hChonJ cells) and irradiated human chondrocytes modified to express TGF-β1 (hChonJb#7 cells). The hChonJ cells were isolated from a polydactyly donor, and TGF-β1 cDNA was delivered to the cells, generating hChonJb#7 cells. Since the cells are allogeneic, the concern of immune response against cells has been raised. In this study, we investigated the immunogenicity of allogenic human chondrocyte, hChonJ cells...
May 18, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28494868/interferon-receptor-signaling-pathways-regulating-pd-l1-and-pd-l2-expression
#19
Angel Garcia-Diaz, Daniel Sanghoon Shin, Blanca Homet Moreno, Justin Saco, Helena Escuin-Ordinas, Gabriel Abril Rodriguez, Jesse M Zaretsky, Lu Sun, Willy Hugo, Xiaoyan Wang, Giulia Parisi, Cristina Puig Saus, Davis Y Torrejon, Thomas G Graeber, Begonya Comin-Anduix, Siwen Hu-Lieskovan, Robert Damoiseaux, Roger S Lo, Antoni Ribas
PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be induced in tumors by interferon exposure, leading to immune evasion. This process is important for immunotherapy based on PD-1 blockade. We examined the specific molecules involved in interferon-induced signaling that regulates PD-L1 and PD-L2 expression in melanoma cells. These studies revealed that the interferon-gamma-JAK1/JAK2-STAT1/STAT2/STAT3-IRF1 axis primarily regulates PD-L1 expression, with IRF1 binding to its promoter...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28488345/patterns-of-pd-1-pd-l1-and-pd-l2-expression-in-pediatric-solid-tumors
#20
Navin Pinto, Julie R Park, Erin Murphy, Jennifer Yearley, Terri McClanahan, Lakshmanan Annamalai, Douglas S Hawkins, Erin R Rudzinski
BACKGROUND: Significant antitumor effects have been observed in a variety of malignancies via blockade of immune checkpoints. Interaction of programmed death 1 (PD-1) with its ligands PD-L1 and PD-L2 suppresses T-cell function and restricts immune-mediated tumor killing. We examined expression of these proteins in children with solid tumors, as expression may serve as biomarkers of response to this class of drugs. METHODS: Sections cut from formalin-fixed paraffin-embedded (FFPE) tissue blocks were processed and evaluated for PD-1, PD-L1, and PD-L2 by immunohistochemistry (IHC) as well as by mRNA expression...
May 10, 2017: Pediatric Blood & Cancer
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