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https://www.readbyqxmd.com/read/29141374/-association-of-pd-1-tim-3-and-trem-1-single-nucleotide-polymorphisms-with-pulmonary-tuberculosis-susceptibility
#1
F M Wang, X Zhang, L Lan, J M Ji, H B Tang, X J Yao, Y Jiang, J Qian, X G Xu, Q Li, P Yao, J H Li, Y P Shen
Objective: To investigate the association of programmed cell death 1(PD-1), T cell immunoglobulin mucin 3 (TIM-3) and triggering receptor expressed on myeloid cells-1 (TREM-1) genes polymorphisms with pulmonary tuberculosis susceptibility. Methods: In this case-control study, peripheral venous blood of 100 pulmonary tuberculosis patients (pulmonary tuberculosis group) in the Jintan People's Hospital of Changzhou and of community physical examination volunteers (health control group) was collected from Mar 2015 to Sep 2016...
November 14, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29139554/immune-checkpoint-inhibitors-new-strategies-to-checkmate-cancer
#2
REVIEW
Ruairi A M Wilson, T R Jeffry Evans, Alasdair R Fraser, Robert J B Nibbs
Immune checkpoint inhibitors (ICIs) targeting Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4) or Programmed cell Death protein 1 (PD-1) receptors have demonstrated remarkable efficacy in subsets of patients with malignant disease. This emerging treatment modality holds great promise for future cancer treatment and has engaged pharmaceutical research interests in tumour immunology. While ICIs can induce rapid and durable responses in some patients, identifying predictive factors for effective clinical responses has proven challenging...
November 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29137242/immune-profiling-of-nf1-associated-tumors-reveals-histologic-subtype-distinctions-and-heterogeneity-implications-for-immunotherapy
#3
Kellie B Haworth, Michael A Arnold, Christopher R Pierson, Kwangmin Choi, Nicholas D Yeager, Nancy Ratner, Ryan D Roberts, Jonathan L Finlay, Timothy P Cripe
Successful treatment of neurofibromatosis type 1 (NF1)-associated tumors poses a significant clinical challenge. While the primary underlying genetic defect driving RAS signaling is well described, recent evidence suggests immune dysfunction contributes to tumor pathogenesis and malignant transformation. As immunologic characterizations, prognostic and predictive of immunotherapeutic clinical response in other cancers, are not fully described for benign and malignant NF1-related tumors, we sought to define their immunologic profiles...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29128969/in-vasculitis-of-small-muscular-arteries-activation-of-vessel-infiltrating-cd8-t-cells-seems-to-be-antigen-independent
#4
Mikiko Kobayashi, Eisaku Ogawa, Ryuhei Okuyama, Hiroyuki Kanno
The etiology of polyarteritis nodosa (PAN) and localized PAN is still unknown, although a T cell-mediated immune mechanism has been considered. CD8 T cells participate not only in the antigen-dependent adaptive immune system, but also in the antigen-independent innate immune system. Non-antigen-activated CD8 T cells express a unique phenotype: granzyme B (GrB) positive /CD25 negative /programmed death-1 (PD-1) negative. The aims of this study were to assess the participation of T cells, especially innate CD8 T cells, in the development of vasculitis...
November 11, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29122656/programmed-death-1-ligands-pd-l1-and-pd-l2-show-distinctive-and-restricted-patterns-of-expression-in-lymphoma-subtypes
#5
Poonam K Panjwani, Vivek Charu, Monique DeLisser, Hernan Molina-Kirsch, Yasodha Natkunam, Shuchun Zhao
The success of immunotherapy using immune checkpoint blockade in solid tumors and in relapsed/refractory classical Hodgkin lymphoma and chronic lymphocytic leukemia holds promise for targeted therapy in hematologic malignancies. Since efficacy of immunomodulatory therapy is correlated with numbers of cells that express programmed death (PD-1) ligands, we evaluated the expression of PD-L1 and PD-L2 proteins using immunohistochemistry in over 702 diagnostic lymphoma biopsies. In classical Hodgkin lymphoma, PD-L1 and PD-L2 were expressed in 82% and 41% of cases respectively, and PD-L1 but not PD-L2 expression correlated with Epstein Barr Virus in tumor cells...
November 6, 2017: Human Pathology
https://www.readbyqxmd.com/read/29118007/pd-1-expression-and-clinical-pd-1-blockade-in-b-cell-lymphomas
#6
Zijun Y Xu-Monette, Jianfeng Zhou, Ken H Young
PD-1 blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/PD-L1 expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1(+) tumor-infiltrating T cells, 9p24 genetic alteration and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORR) of 65-87% and durable disease control in phase I/II clinical trials...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29117898/the-contribution-of-immune-infiltrates-and-the-local-microenvironment-in-the-pathogenesis-of-osteosarcoma
#7
Marie-Françoise Heymann, Frédéric Lézot, Dominique Heymann
Osteosarcoma is a rare primary bone cancer characterized by cancer cells producing calcified osteoid extracellular matrix and inducing lung metastases with a high frequency. The local microenvironment defined several tumor niches controlling the tumor growth and cell extravasation. The immune infiltrate composes one of these niches. The immune environment of osteosarcoma is mainly composed by T-lymphocytes and macrophages but also contains other subpopulations including B-lymphocytes and mast cells. Osteosarcoma cells control the recruitment and differentiation of immune infiltrating cells and establish a local immune tolerant environment favorable to the tumor growth, drug resistance and the occurrence of metastases...
November 2, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29112124/gene-regulatory-network-rewiring-in-the-immune-cells-associated-with-cancer
#8
Pengyong Han, Chandrasekhar Gopalakrishnan, Haiquan Yu, Edwin Wang
The gene regulatory networks (GRNs) of immune cells not only indicate cell identity but also reveal the dynamic changes of immune cells when comparing their GRNs. Cancer immunotherapy has advanced in the past few years. Immune-checkpoint blockades (i.e., blocking PD-1, PD-L1, or CTLA-4) have shown durable clinical effects on some patients with various advanced cancers. However, major gaps in our knowledge of immunotherapy have been recognized. To fill these gaps, we conducted a systematic analysis of the GRNs of key immune cell subsets (i...
November 7, 2017: Genes
https://www.readbyqxmd.com/read/29112015/pd-l1-and-pd-l2-are-differentially-expressed-by-macrophages-or-tumor-cells-in-primary-cutaneous-diffuse-large-b-cell-lymphoma-leg-type
#9
Sarah Menguy, Martina Prochazkova-Carlotti, Marie Beylot-Barry, Fréderic Saltel, Béatrice Vergier, Jean-Philippe Merlio, Anne Pham-Ledard
As checkpoint molecules' inhibition may represent a therapeutic option in relapsing cases, we assessed programmed death ligands' (PD-L1/PD-L2) expression in a series of 29 primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) cases. Double immunostaining for either PD-L1 or PD-L2 was associated either with PAX5 staining to evaluate tumor cells or with CD68 or CD163 staining for macrophages. The microenvironment of PCDLBCL-LT was characterized by immunostainings for CD3 (tumor-infiltrating lymphocytes), FOXP3 (regulatory T cells), programmed cell death-1, and CD33 (myeloid-derived suppressor cells)...
November 3, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29111220/pd-1-hi-cxcr5-cd4-tfh-cells-play-defense-in-cancer-and-offense-in-arthritis
#10
Chunyan Gu-Trantien, Karen Willard-Gallo
T follicular helper (TFH) cells are characteristically defined by their CXCR5 positivity and homing to B cell follicles in secondary lymphoid organs (SLO). An expanded subpopulation of functionally comparable and phenotypically similar PD-1(hi)CXCR5(-)CD4(+) T cells were recently identified in breast cancer (BC) and rheumatoid arthritis (RA) to have beneficial or detrimental roles, respectively, but are they inflammatory tissue effector TFH cells?
October 27, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/29103968/anti-pd-l1-tgf%C3%AE-r2-m7824-fusion-protein-induces-immunogenic-modulation-of-human-urothelial-carcinoma-cell-lines-rendering-them-more-susceptible-to-immune-mediated-recognition-and-lysis
#11
Italia Grenga, Renee N Donahue, Morgan L Gargulak, Lauren M Lepone, Mario Roselli, Marijo Bilusic, Jeffrey Schlom
BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. M7824 is a novel first-in-class bifunctional fusion protein comprising a monoclonal antibody against programmed death-ligand 1 (PD-L1, avelumab), fused to the extracellular domain of human transforming growth factor beta (TGFβ) receptor 2, which functions as a TGFβ "trap." Advanced urothelial tumors have been shown to express TGFβ, which possesses immunosuppressive properties that promote cancer progression and metastasis...
November 2, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29100036/nafamostat-mesilate-a-serine-protease-inhibitor-suppresses-interferon-gamma-induced-up-regulation-of-programmed-cell-death-ligand-1-in-human-cancer-cells
#12
Sadamu Homma, Kazumi Hayashi, Kosaku Yoshida, Yukiko Sagawa, Yuko Kamata, Masaki Ito
Programmed cell death ligand-1 (PD-L1) plays a pivotal role in the suppression of antitumour immunity by binding to programmed cell death-1 (PD-1) on tumouricidal cytotoxic T lymphocytes (CTLs), rendering them inactive. As blockade of PD-1/PD-L1 interaction by the monoclonal antibodies induced effective T cell-mediated antitumour response, suppression of PD-L1 expression in tumour cells by the chemical agent might contribute to treatment against malignant tumours. Nafamostat mesilate (NM), a serine protease inhibitor that is frequently used in the clinic, potently suppressed interferon-gamma (IFN-gamma)-induced up-regulation of PD-L1 in cultured human lung cancer cells (HLC-1) at both the messenger RNA (mRNA) and protein levels...
October 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29097422/intratumoral-cd8-t-cell-apoptosis-is-a-major-component-of-t-cell-dysfunction-and-impedes-anti-tumor-immunity
#13
Brendan L Horton, Jason B Williams, Alexandra Cabanov, Stefani Spranger, Thomas F Gajewski
Subsets of human tumors are infiltrated with tumor antigen-specific CD8(+) T cells (TILs) despite tumor progression. These TILs are thought to be inactivated by the immunosuppressive tumor microenvironment, through the engagement of inhibitory receptors such as CTLA-4 and PD-1. However, antigen-specific CD8+ TILs are not functionally inert, but are undergoing activation in situ. Here, we show that antigen-specific CD8(+) TIL are actively proliferating, yet also undergo high rates of apoptosis, leading to a vicious cycle of activation and death that limits immune efficacy...
November 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29074606/low-pd-1-expression-in-cytotoxic-cd8-tumor-infiltrating-lymphocytes-confers-an-immune-privileged-tissue-microenvironment-in-nsclc-with-a-prognostic-and-predictive-value
#14
Giulia Mazzaschi, Denise Madeddu, Angela Falco, Giovanni Bocchialini, Matteo Goldoni, Francesco Sogni, Giovanna Armani, Costanza Annamaria Lagrasta, Bruno Lorusso, Chiara Maria Mangiaracina, Rocchina Vilella, Caterina Frati, Roberta R Alfieri, Luca Ampollini, Michele Veneziani, Enrico M Silini, Andrea Ardizzoni, Konrad Urbanek, Franco Aversa, Federico Quaini, Marcello Tiseo
The success of immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. To determine whether distinct tissue immune microenvironments differentially impact on clinical outcome in Non Small Cell Lung Cancer (NSCLC), an extended analysis of PD-L1 and Tumor Infiltrating Lymphocytes (TILs) was performed. Experimental Design Samples from resected adenocarcinoma (ADC 42) and squamous cell carcinoma (SCC 58) and from 26 advanced diseases (13 ADC, 13 SCC) treated with nivolumab were analyzed...
October 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29069649/the-systemic-activation-of-programmed-death-1-pd-l1-axis-protects-systemic-lupus-erythematosus-model-from-nephritis
#15
Wenjun Liao, Hua Zheng, Sha Wu, Yanmei Zhang, Wei Wang, Zili Zhang, Chenfei Zhou, Hongjun Wu, Jie Min
BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by abnormal activated T cells, autoreactive B cells, and massive cytokines. The CD4+ T cells determined B-cells differentiation and cytokines production. The programmed death 1 (PD-1) is the checkpoint immunoinhibitory receptor of activated T cells, and its engagement could exhaust T cells. In this study, we investigated the role of PD-1 systemic engagement with PD-L1-Ig in lupus-like nephritis in SLE mice. METHODS: The murine PD-L1-Ig was injected into SLE-prone mice...
October 26, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/29069274/undifferentiated-pancreatic-carcinomas-display-enrichment-for-frequency-and-extent-of-pd-l1-expression-by-tumor-cells
#16
Heidi D Lehrke, Rondell P Graham, Robert R McWilliams, Dora M Lam-Himlin, Thomas C Smyrk, Sarah Jenkins, Haidong Dong, Lizhi Zhang
Objectives: Programmed death ligand 1 (PD-L1) expression in pancreatic ductal adenocarcinoma (PDA) has been described, but unselected PDAs have shown limited clinical responsiveness to anti-programmed death 1 (PD-1)/PD-L1 therapy. Methods: We studied 24 cases of undifferentiated pancreatic carcinoma (UPC) using immunohistochemistry for PD-L1 (E1L3N clone), CD3, CD20, CD68, and DNA mismatch repair proteins in this study. Slides were scored for extent of PD-L1 expression on tumor cells and tumor-infiltrating immune cells...
November 2, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29065979/not-all-immune-checkpoint-inhibitors-are-created-equal-meta-analysis-and-systematic-review-of-immune-related-adverse-events-in-cancer-trials
#17
REVIEW
B El Osta, F Hu, R Sadek, R Chintalapally, S-C Tang
BACKGROUND: Targeting immune checkpoints is a novel approach in cancer therapy. This strategy may trigger immune related adverse events (irAE). We hypothesize that the incidence of irAE will be greater in patients receiving immune checkpoint inhibitors (ICI) targeting only immune cells compared to those that also target tumor cells (PD-L1). In addition, we compared the specific irAE profile and overall response rate (ORR) for each ICI by target(s). MATERIALS AND METHODS: We reviewed all ICI cancer clinical trials (90; 174 arms) that reported irAE and were published through MEDLINE...
November 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29063177/approach-to-richter-transformation-of-chronic-lymphocytic-leukemia-in-the-era-of-novel-therapies
#18
REVIEW
Maliha Khan, Rabbia Siddiqi, Philip A Thompson
Chronic lymphocytic leukemia (CLL) has a highly variable clinical course. About 2-10% of CLL patients develop aggressive histological transformation, most commonly to diffuse large B cell lymphoma (DLBCL), historically called Richter transformation (RT). Clinical features suggestive of RT include elevated LDH and non-specific symptoms such as fever, weight loss, and lymphadenopathy. 18-fluorodeoxyglucose (18-FDG) uptake is increased on PET scan (standardized uptake value max most commonly ≥ 10). PET/CT study can identify optimal site for excisional biopsy, which is the gold standard for RT diagnosis, as well as aid in disease staging and prognostication...
October 23, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29058791/in-vitro-and-in-vivo-effect-of-pd-1-pd-l1-blockade-on-microglia-macrophage-activation-and-t-cell-subset-balance-in-cryptococcal-meningitis
#19
Yuan-Mei Che, Yi Zhang, Ming Li, Xiao-Peng Li, Lun-Li Zhang
This study aimed to investigate the PD-1/ PD-L1 signaling pathway and its effects the activation of microglia/macrophage and balancing T cell subsets in cryptococcal meningitis (CM). A total of 126 CM patients and 126 healthy individuals were recruited for the study. The CM patients were treated with amphotericin B (AmB). Seventy five C57BL/6 mice were grouped into the normal control, CM model, CM + AmB, sham and CM + PD-1 antibodies (Ab) groups. CD4(+) and CD8(+) T cells as well as microglia/macrophages were analyzed by means of flow cytometry...
October 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29055015/small-molecule%C3%A2-inhibition-of-pd-1-transcription-is-an-effective-alternative-to-antibody-blockade-in-cancer-therapy
#20
Alison Taylor, David Rothstein, Christopher E Rudd
The impact of PD-1 immune checkpoint therapy prompts exploration of other strategies to downregulate PD-1 for cancer therapy. We previously showed that the serine/threonine kinase, glycogen synthase kinase GSK-3α/β, is a central regulator of PD-1 transcription in CD8+ T cells. Here, we show that the use of small molecule inhibitors of GSK-3α/β (GSK-3i) to reduce pcdc1 (PD-1) transcription and expression was as effective as anti-PD-1 and PDL-1 blocking antibodies in the control of B16 melanoma, or EL4 lymphoma, in primary tumor and metastatic settings...
October 20, 2017: Cancer Research
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