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https://www.readbyqxmd.com/read/27924827/pd-1-pd-l-pathway-inhibits-m-tb-specific-cd4-t-cell-functions-and-phagocytosis-of-macrophages-in-active-tuberculosis
#1
Lei Shen, Yan Gao, Yuanyuan Liu, Bingyan Zhang, Qianqian Liu, Jing Wu, Lin Fan, Qinfang Ou, Wenhong Zhang, Lingyun Shao
The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921410/downregulation-of-immunosuppressive-molecules-pd-1-and-pd-l1-but-not-pd-l2-in-the-patients-with-multiple-sclerosis
#2
Mohammad Reza Javan, Saeed Aslani, Mohammad Reza Zamani, Javad Rostamnejad, Milad Asadi, Mahdi Farhoodi, Mohammad Hossein Nicknam
Programmed cell death-1 (PD-1) and its ligands, PD-L1 and PD-L2, have been regarded as important immune system regulatory molecules. The aberrant expression of the molecules has been related to several autoimmune disorders. This study is aimed to assess the mRNA expression level of PD-1, PD-L1, and PD-L2 molecules in the peripheral blood mononuclear mells (PBMCs) from multiple sclerosis (MS) patients. PBMCs were isolated from the whole blood of 50 MS and 50 healthy individuals. Total RNA content of the leukocytes was extracted...
August 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27881581/nivolumab-in-the-treatment-of-hodgkin-lymphoma
#3
Stephen M Ansell
Despite an extensive immune infiltrate that is recruited to the tumor by malignant Reed Sternberg cells in Hodgkin lymphoma, the antitumor immune response is ineffective and unable to eradicate the malignant cells. The ineffective immune response is in part due to PD-1 signaling that renders intratumoral immune cells anergic. Reed Sternberg cells have been shown to upregulate expression of the PD-1 ligands, PD-L1 and PD-L2, due to either genetic alterations at chromosome 9p24.1 or Epstein Barr virus infection, and these ligands suppress the function of PD-1+ intratumoral T-cells...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27870715/posttranscriptional-control-of-pd-l1-expression-by-17%C3%AE-estradiol-via-pi3k-akt-signaling-pathway-in-er%C3%AE-positive-cancer-cell-lines
#4
Lingyun Yang, Feng Huang, Jiandong Mei, Xun Wang, Qiuyang Zhang, Hongjing Wang, Mingrong Xi, Zongbing You
OBJECTIVE: Estrogen is a well-known oncogenic driver in endometrial (ECs) and breast cancers (BCs). Programmed cell death protein 1 (PD-1) and its ligands PD-1 Ligand 1 (PD-L1) and PD-L2 have been shown to mediate immune evasion of the tumor cells. The purpose of the present study was to assess the effects of estrogen on PD-L1 and PD-L2 expression in EC and BC cell lines. METHODS: 17β-Estradiol (E2)-induced expression of PD-L1 and PD-L2 and possible signaling pathway were investigated in EC and BC cells...
November 17, 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27867382/il-1%C3%AE-but-not-programed-death-1-and-programed-death-ligand-pathway-is-critical-for-the-human-th17-response-to-mycobacterium-tuberculosis
#5
Emmanuel Stephen-Victor, Varun Kumar Sharma, Mrinmoy Das, Anupama Karnam, Chaitrali Saha, Maxime Lecerf, Caroline Galeotti, Srinivas V Kaveri, Jagadeesh Bayry
The programed death-1 (PD-1)-programed death ligand-1 (PD-L1) and PD-L2 co-inhibitory pathway has been implicated in the evasion strategies of Mycobacterium tuberculosis. Specifically, M. tuberculosis-induced PD-L1 orchestrates expansion of regulatory T cells and suppression of Th1 response. However, the role of PD pathway in regulating Th17 response to M. tuberculosis has not been investigated. In the present report, we demonstrate that M. tuberculosis and M. tuberculosis-derived antigen fractions have differential abilities to mediate human monocyte- and dendritic cell (DC)-mediated Th17 response and were independent of expression of PD-L1 or PD-L2 on aforementioned antigen-presenting cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27861596/pd-l1-status-in-refractory-lymphomas
#6
Semir Vranic, Nilanjan Ghosh, Jeffery Kimbrough, Nurija Bilalovic, Ryan Bender, David Arguello, Yvonne Veloso, Aida Dizdarevic, Zoran Gatalica
Targeted immunotherapy based on PD-1/PD-L1 suppression has revolutionized the treatment of various solid tumors. A remarkable improvement has also been observed in the treatment of patients with refractory/relapsing classical Hodgkin lymphoma (cHL). We investigated PD-L1 status in a variety of treatment resistant lymphomas. Tumor samples from 78 patients with therapy resistant lymphomas were immunohistochemically (IHC) investigated for the expression of PD-L1 using two antibody clones (SP142 and SP263, Ventana)...
2016: PloS One
https://www.readbyqxmd.com/read/27837027/association-of-pd-1-pd-l-axis-expression-with-cytolytic-activity-mutational-load-and-prognosis-in-melanoma-and-other-solid-tumors
#7
Ludmila Danilova, Hao Wang, Joel Sunshine, Genevieve J Kaunitz, Tricia R Cottrell, Haiying Xu, Jessica Esandrio, Robert A Anders, Leslie Cope, Drew M Pardoll, Charles G Drake, Janis M Taube
Programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint blockade has led to remarkable and durable objective responses in a number of different tumor types. A better understanding of factors associated with the PD-1/PD-L axis expression is desirable, as it informs their potential role as prognostic and predictive biomarkers and may suggest rational treatment combinations. In the current study, we analyzed PD-L1, PD-L2, PD-1, and cytolytic activity (CYT) expression, as well as mutational density from melanoma and eight other solid tumor types using The Cancer Genome Atlas database...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27783986/pd-l2-negatively-regulates-th1-mediated-immunopathology-during-fasciola-hepatica-infection
#8
Cinthia C Stempin, Claudia C Motrán, María P Aoki, Cristian R Falcón, Fabio M Cerbán, Laura Cervi
Macrophage plasticity is critical for controlling inflammation including those produced by helminth infections, where alternatively activated macrophages (AAM) are accumulated in tissues. AAM expressing the co-inhibitory molecule programmed death ligand 2 (PD-L2), which is capable of binding programmed death 1 (PD-1) expressed on activated T cells, have been demonstrated in different parasitic infections. However, the role of PD-L2 during F. hepatica infection has not yet been explored. We observed that F. hepatica infection or a F...
October 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27757309/intra-tumoral-heterogeneity-in-the-expression-of-programmed-death-pd-ligands-in-isogeneic-primary-and-metastatic-lung-cancer-implications-for-immunotherapy
#9
David J Pinato, Robert J Shiner, Solomon D T White, James R M Black, Pritesh Trivedi, Justin Stebbing, Rohini Sharma, Francesco A Mauri
Purpose: There is inconclusive evidence to suggest the expression of programmed cell death (PD) ligand 1 (PD-L1) is a putative predictor of response to PD-1/PD-L1-targeted therapies in lung cancer. We evaluated the heterogeneity in the expression of PD-1 ligands in isogeneic primary and metastatic LC specimens. Experimental Design: From 12,580 post mortem cases, we identified 214 patients with untreated metastatic LC, of which 98 had adequately preserved tissues to construct a syngeneic primary LC/metastasis tissue microarray...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27757299/intratumoral-expression-levels-of-pd-l1-gzma-and-hla-a-along-with-oligoclonal-t-cell-expansion-associate-with-response-to-nivolumab-in-metastatic-melanoma
#10
Hiroyuki Inoue, Jae-Hyun Park, Kazuma Kiyotani, Makda Zewde, Azusa Miyashita, Masatoshi Jinnin, Yukiko Kiniwa, Ryuhei Okuyama, Ryota Tanaka, Yasuhiro Fujisawa, Hiroshi Kato, Akimichi Morita, Jun Asai, Norito Katoh, Kenji Yokota, Masashi Akiyama, Hironobu Ihn, Satoshi Fukushima, Yusuke Nakamura
Immune checkpoint inhibitors blocking the interaction between programmed death-1 (PD-1) and PD-1 ligand-1 (PD-L1) are revolutionizing the cancer immunotherapies with durable clinical responses. Although high expression of PD-L1 in tumor tissues has been implicated to correlate with the better response to the anti-PD-1 therapies, this association has been controversial. In this study, to characterize immune microenvironment in tumors, we examined mRNA levels of immune-related genes and characterized T cell repertoire in the tumors of 13 melanoma patients before and after nivolumab treatment...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27737878/classical-hodgkin-lymphoma-with-reduced-%C3%AE-2m-mhc-class-i-expression-is-associated-with-inferior-outcome-independent-of-9p24-1-status
#11
Margaretha G M Roemer, Ranjana H Advani, Robert A Redd, Geraldine S Pinkus, Yasodha Natkunam, Azra H Ligon, Courtney F Connelly, Christine J Pak, Christopher D Carey, Sarah E Daadi, Bjoern Chapuy, Daphne de Jong, Richard T Hoppe, Donna S Neuberg, Margaret A Shipp, Scott J Rodig
In classical Hodgkin Lymphoma (cHL), malignant Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple mechanisms, including perturbed antigen presentation and enhanced PD-1 signaling. HRS cell expression of the PD-1 ligands is attributable, in part, to copy number alterations of 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2) Amplification of PD-L1/PD-L2 is associated with advanced clinical stage and inferior progression-free survival (PFS) following frontline (induction) therapy. The relationships between altered expression of β2-microglobulin (β2M), MHC class I, and MHC class II by HRS cells, PD-L1/PD-L2 amplification, and clinical outcome in cHL are poorly defined...
October 13, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27736779/nonencapsulated-trichinella-pseudospiralis-infection-impairs-follicular-helper-t-cell-differentiation-with-subclass-selective-decreases-in-antibody-responses
#12
Kazunobu Asano, Zhiliang Wu, Piyarat Srinontong, Takahide Ikeda, Isao Nagano, Hirokuyi Morita, Yoichi Maekawa
Infectious microorganisms often modify host immunity to escape from immune elimination. Trichinella is a unique nematode of the helminth family, whose members parasitize the muscle cells inside the host without robust eliminative reactions. There are several species of Trichinella; some develop in muscle cells that become encapsulated (e.g., Trichinella spiralis) and others in cells that do not encapsulate (e.g., Trichinella pseudospiralis). It has already been established that Trichinella infection affects host immune responses in several experimental immune diseases in animal models; however, most of those studies were done using T...
December 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27727484/comparison-of-tumour-infiltrating-lymphocytes-between-primary-and-metastatic-tumours-in-breast-cancer-patients
#13
Rin Ogiya, Naoki Niikura, Nobue Kumaki, Giampaolo Bianchini, Shigehisa Kitano, Takayuki Iwamoto, Naoki Hayashi, Kozue Yokoyama, Risa Oshitanai, Mayako Terao, Toru Morioka, Banri Tsuda, Takuho Okamura, Yuki Saito, Yasuhiro Suzuki, Yutaka Tokuda
The presence of tumour-infiltrating lymphocytes (TILs) is associated with favourable long-term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumours escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumours. We retrospectively identified 25 patients with human epidermal growth factor receptor-2 (HER2)-positive (n = 14, HER2+) and triple negative (n = 11, TN) early breast cancer diagnosed during 1990-2009 at Tokai University Hospital and who subsequently experienced regional or distant recurrence confirmed by tumour biopsy/resection...
October 11, 2016: Cancer Science
https://www.readbyqxmd.com/read/27677953/epstein-barr-virus-associated-gastric-cancer-and-potential-mechanisms-of-oncogenesis
#14
Ezequiel M Fuentes-Pananá, Abigail Morales-Sánchez
EBV-associated Gastric Cancer (EBVaGC) comprises about 9% of all cases of GC and constitutes a distinct clinicopathological and molecular entity. The pattern of viral expression in EBVaGC cannot be set to any of the previously EBV-associated malignancies. Several lines of evidence support that viral expression in EBVaGC is characterized by high transcription of the BamH1-A rightward transcript (BART), low-levels of EBNA-1 and lack of LMP1. The high transcription activity of the BamH1-A region is importantly directed to express BART miRNAs, supporting a critical role for these miRNAs during epithelial cell infection and carcinogenesis...
September 26, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27671847/mesenchymal-stromal-cell-secretion-of-programmed-death-1-ligands-regulates-t-cell-mediated-immunosuppression
#15
Lindsay C Davies, Nina Heldring, Nadir Kadri, Katarina Le Blanc
Mesenchymal stromal cells (MSCs) exert broad immunosuppressive potential, modulating the activity of cells of innate and adaptive immune systems. As MSCs become accepted as a therapeutic option for the treatment of immunological disorders such as Graft versus Host Disease, our need to understand the intricate details by which they exert their effects is crucial. Programmed death-1 (PD-1) is an important regulator in T cell activation and homeostatic control. It has been reported that this pathway may be important in contact-dependent mediated immunomodulation by MSCs...
September 27, 2016: Stem Cells
https://www.readbyqxmd.com/read/27665733/pd-1-t-cells-inhibit-effector-t-cells-at-the-pathologic-site-of-miliary-tuberculosis
#16
Amar Singh, Anant Mohan, Aprajit B Dey, Dipendra K Mitra
BACKGROUND: Optimal T cell activation is vital for the successful resolution of microbial infections. Programmed death-1 (PD-1) is key immune checkpoint receptor expressed by activated T cells. Aberrant/excessive inhibition mediated by PD-1 may impair host immunity to M. tuberculosis infection, leading to disseminated disease like miliary tuberculosis (MTB). PD-1 mediated inhibition of T cells in pulmonary tuberculosis and TB pleurisy is reported. However, their role in MTB, particularly at the pathologic sites remains to be addressed...
September 26, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27660198/pd-1-pd-l-and-autoimmunity-a-growing-relationship
#17
Mohammad Reza Zamani, Saeed Aslani, Arash Salmaninejad, Mohammad Reza Javan, Nima Rezaei
Programmed death 1 (PD-1) and its ligands, namely PD-L1 and PD-L2, are one of the key factors responsible for inhibitory T cell signaling, mediating the mechanisms of tolerance and providing immune homeostasis. Mounting evidence demonstrates that impaired PD-1:PD-L function plays an important role in a variety of autoimmune diseases such as Type 1 diabetes (T1D), encephalomyelitis, inflammatory bowel diseases (IBD), Rheumatoid Arthritis (RA), autoimmune hepatitis (AIH), Behcet's disease (BD), myasthenia gravis (MG), autoimmune uveitis (AU), Sjögren's syndrome (SjS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), myocarditis, and ankylosing spondylitis (AS)...
September 15, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27649554/the-t-cell-receptor-repertoire-influences-the-tumor-microenvironment-and-is-associated-with-survival-in-aggressive-b-cell-lymphoma
#18
Colm Keane, Clare Gould, Kimberley Jones, David Hamm, Dipti Talaulikar, Jonathan Ellis, Frank Vari, Simone Birch, Erica Han, Peter Wood, Kim-Anh Le Cao, Michael R Green, Pauline Crooks, Sanjiv Jain, Joshua Tobin, Raymond J Steptoe, Maher K Gandhi
PURPOSE: To investigate the relationship between the intra-tumoral T-cell receptor (TCR) repertoire and the tumor microenvironment (TME) in de novo Diffuse Large B-cell Lymphoma (DLBCL), and the TCR's impact on survival. EXPERIMENTAL DESIGN: We performed high-throughput unbiased TCRBeta sequencing on a population based cohort of 92 DLBCL patients treated with conventional (i.e. non-checkpoint blockade) frontline 'R-CHOP' therapy. Key immune checkpoint genes within the TME were digitally quantified by nanoString{trade mark, serif}...
September 20, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27622019/myeloid-pten-deficiency-impairs-tumor-immune-surveillance-via-immune-checkpoint-inhibition
#19
M Kuttke, E Sahin, J Pisoni, S Percig, A Vogel, D Kraemmer, L Hanzl, J S Brunner, H Paar, K Soukup, A Halfmann, A M Dohnal, C W Steiner, S Blüml, J Basilio, B Hochreiter, M Salzmann, B Hoesel, G Lametschwandtner, R Eferl, J A Schmid, G Schabbauer
Tumor-host interaction is determined by constant immune surveillance, characterized by tumor infiltration of myeloid and lymphoid cells. A malfunctioning or diverted immune response promotes tumor growth and metastasis. Recent advances had been made, by treating of certain tumor types, such as melanoma, with T-cell checkpoint inhibitors. This highlights the importance of understanding the molecular mechanisms underlying the crosstalk between tumors and their environment, in particular myeloid and lymphoid cells...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27609582/-increased-expressions-of-programmed-death-1-pd-1-and-its-ligands-in-peripheral-cd3-t-cells-and-cd19-b-cells-in-patients-with-hepatocellular-carcinoma
#20
Wei Liu, Lin Chai, Junli Liang, Zhizhong Lu, Siwei Yang
Objective To investigate the changes of programmed death 1 (PD-1) and ligands, as well as interferon-γ (IFN-γ) in peripheral blood mononuclear cells (PBMCs) of patients with hepatocellular carcinoma (HCC). Methods The peripheral blood was collected from 15 early HCC patients, 13 progressive HCC patients and 12 healthy volunteers. PBMCs was isolated from the peripheral blood. The expressions of PD-1, PD-L1 and PD-L2 in PBMCs were detected by flow cytometry; the serum level of IFN-γ was determined by ELISA; the correlation of PD-1 and IFN-γ was analyzed with Pearson's correlation and One-way ANOVA...
September 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
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