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PD-1 B cell

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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
#1
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/28533941/changes-in-clinical-laboratory-parameters-and-pharmacodynamic-markers-in-response-to-blinatumomab-treatment-of-patients-with-relapsed-refractory-all
#2
Virginie Nägele, Andrea Kratzer, Gerhard Zugmaier, Chris Holland, Youssef Hijazi, Max S Topp, Nicola Gökbuget, Patrick A Baeuerle, Peter Kufer, Andreas Wolf, Matthias Klinger
BACKGROUND: Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study. METHODS: Data from 36 adults with relapsed/refractory ALL receiving blinatumomab as 4-week continuous IV infusions in various dose cohorts were analyzed for changes in liver enzymes, first-dose parameters, peripheral blood cell subpopulations, and cytokine/granzyme B release...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#3
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28525897/a-cellular-platform-for-the-evaluation-of-immune-checkpoint-molecules
#4
Sabrina Jutz, Annika Hennig, Wolfgang Paster, Ömer Asrak, Dejana Dijanovic, Florian Kellner, Winfried F Pickl, Johannes B Huppa, Judith Leitner, Peter Steinberger
Blockade of the T cell coinhibitory molecules CTLA-4 and PD-1 has clinical utility to strengthen T cell responses. In addition to these immune checkpoints an ever-growing number of molecules has been implicated in generating coinhibitory signals in T cells. However, investigating coinhibitory molecules in primary human cells is complicated by the restricted expression and promiscuity of both coinhibitory receptors and their ligands. Here we have evaluated the potential of fluorescence-based transcriptional reporters based on the human Jurkat T cell line in conjunction with engineered T cell stimulator cell lines for investigating coinhibitory pathways...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515726/comparative-analysis-of-immune-checkpoint-molecules-and-their-potential-role-in-the-transmissible-tasmanian-devil-facial-tumor-disease
#5
Andrew S Flies, Nicholas B Blackburn, Alan Bruce Lyons, John D Hayball, Gregory M Woods
Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28510571/second-line-pazopanib-in-patients-with-relapsed-and-refractory-small-cell-lung-cancer-a-multicentre-phase-ii-study-of-the-hellenic-oncology-research-group
#6
F Koinis, S Agelaki, V Karavassilis, N Kentepozidis, E Samantas, S Peroukidis, P Katsaounis, E Hartabilas, I I Varthalitis, I Messaritakis, G Fountzilas, V Georgoulias, A Kotsakis
BACKGROUND: Pazopanib is a tyrosine kinase inhibitor with antiangiogenic activity. Vascular endothelial growth factor expression is increased in SCLC and is correlated with poor prognosis. The efficacy and tolerance of second-line pazopanib in SCLC was evaluated. PATIENTS AND METHODS: Patients with platinum-sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were enrolled in a multicentre phase II study. The primary end point was the progression-free survival rate (PFS-R) at week 8 in each cohort...
May 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28507813/deep-exploration-of-the-immune-infiltrate-and-outcome-prediction-in-testicular-cancer-by-quantitative-multiplexed-immunohistochemistry-and-gene-expression-profiling
#7
Peter J Siska, Romany A N Johnpulle, Alice Zhou, Jennifer Bordeaux, Ju Young Kim, Bashar Dabbas, Naveen Dakappagari, Jeffrey C Rathmell, W Kimryn Rathmell, Alicia K Morgans, Justin M Balko, Douglas B Johnson
Platinum-based chemotherapy is usually curative for patients with testicular germ cell tumors (TGCT), but a subset of patients experience disease progression and poor clinical outcomes. Here, we tested whether immune profiling of TGCT could identify novel prognostic markers and therapeutic targets for this patient cohort. We obtained primary and metastatic TGCT samples from one center. We performed immune profiling using multiplexed fluorescence immunohistochemistry (FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression profiling (Nanostring nCounter Immune panel)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28504999/tumor-microenvironment-and-checkpoint-molecules-in-primary-cutaneous-diffuse-large-b-cell-lymphoma-new-therapeutic-targets
#8
Christina Mitteldorf, Arbeneshe Berisha, Monique C Pfaltz, Sigrid M C Broekaert, Michael P Schön, Katrin Kerl, Werner Kempf
Programmed death ligand 1 (PD-L1) is expressed by 20% to 57% of systemic diffuse large B cell lymphomas (DLBCLs). PD-L1 expression in primary cutaneous DLBCL (pcDLBCL) has not been studied so far. Sixteen paraffin-embedded tissue samples of pcDLBCL (13 leg type [LT], 3 others [OT]) were investigated for PD-1, PD-L1, and CD33 expression and the cellular composition of the tumor microenvironment, focusing on myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. Membrane-bound PD-L1 expression by the tumor cells was observed in all samples, albeit to a variable extent (19...
May 12, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28497159/current-status-of-chimeric-antigen-receptor-engineered-t-cell-based-and-immune-checkpoint-blockade-based-cancer-immunotherapies
#9
REVIEW
Upendra P Hegde, Bijay Mukherji
Adoptive cell therapies with chimeric antigen receptor (CAR) engineered T cells (CAR-T) and immune checkpoint inhibition (ICI)-based cancer immunotherapies have lately shown remarkable success in certain tumor types. CAR-T cell-based therapies targeting CD19 can now induce durable remissions as well as prolong disease-free survival of patients with CD19 positive treatment refractory B cell malignancies and ICI-based therapies with humanized monoclonal antibodies against the T cell inhibitory receptors CTLA-4 and PD-1 as well as against the PD-1 ligand, PD-L1, can now achieve durable remissions as well as prolongation of life of a sizeable fraction of patients with melanoma and Hodgkin's lymphoma and non-small cell cancers...
May 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28496056/stat3-inhibitor-abrogates-the-expression-of-pd-1-ligands-on-lymphoma-cell-lines
#10
Chaoya Ma, Hasita Horlad, Cheng Pan, Hiromu Yano, Koji Ohnishi, Yukio Fujiwara, Masao Matsuoka, Aeju Lee, Takuro Niidome, Ryuya Yamanaka, Motohiro Takeya, Yoshihiro Komohara
Recent studies have indicated the significance of immune checkpoint molecules including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4, and T-cell immunoglobulin and mucin domain-containing molecule-3 for anti-tumor immune responses. We previously investigated PD-1 ligand 1/2 (PD-L1/2) expression in lymphoma cell lines, and found that PD-L1/2 is expressed on the adult T-cell leukemia/lymphoma (ATL-T) and B-cell lymphoma (SLVL) cell lines. In the present study, we investigated whether the Stat3 inhibitor WP1066 abrogated PD-L1/2 expression in lymphoma cell lines...
May 10, 2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28490569/safety-tolerability-of-pembrolizumab-in-patients-with-relapsed-refractory-primary-mediastinal-large-b-cell-lymphoma
#11
Pier Luigi Zinzani, Vincent Ribrag, Craig H Moskowitz, Jean-Marie Michot, John Kuruvilla, Arun Balakumaran, Yayan Zhang, Sabine Chlosta, Margaret A Shipp, Philippe Armand
Treatment options for relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL) are limited and prognosis is generally poor (overall response rate [ORR] 0-25%; 2-year overall survival 15%). PMBCL frequently involves PD-1 ligand overexpression, potentially making PMBCL particularly susceptible to PD-1 blockade. We evaluated safety and antitumor activity of pembrolizumab, an anti-PD-1 antibody, in rrPMBCL as part of the KEYNOTE-013 multicohort Phase 1b trial. At time of data cutoff, 18 patients (median age 30; median 3 prior lines of therapy) had been enrolled and treated, of whom 17 were included in the efficacy analyses...
May 10, 2017: Blood
https://www.readbyqxmd.com/read/28484017/structural-basis-for-cancer-immunotherapy-by-the-first-in-class-checkpoint-inhibitor-ipilimumab
#12
Udupi A Ramagopal, Weifeng Liu, Sarah C Garrett-Thomson, Jeffrey B Bonanno, Qingrong Yan, Mohan Srinivasan, Susan C Wong, Alasdair Bell, Shilpa Mankikar, Vangipuram S Rangan, Shrikant Deshpande, Alan J Korman, Steven C Almo
Rational modulation of the immune response with biologics represents one of the most promising and active areas for the realization of new therapeutic strategies. In particular, the use of function blocking monoclonal antibodies targeting checkpoint inhibitors such as CTLA-4 and PD-1 have proven to be highly effective for the systemic activation of the human immune system to treat a wide range of cancers. Ipilimumab is a fully human antibody targeting CTLA-4 that received FDA approval for the treatment of metastatic melanoma in 2011...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28482188/pregnancy-favors-the-expansion-of-circulating-functional-follicular-helper-t-cells
#13
Clarice Monteiro, Taissa M Kasahara, José Roberto Castro, Priscila M Sacramento, Joana Hygino, Newton Centurião, Tatiane Cassano, Lana M Ferreira Lopes, Simone Leite, Vander Guimarães Silva, Sudhir Gupta, Cleonice A M Bento
Pregnancy favors antibody production, and some evidence has suggested a direct effect of estrogen on B cells. The impact of pregnancy on circulating follicular helper T (TFH) cells, typically identified by the expression of CD45RO and CXCR5, has not been previously investigated. Here, the percentage of TFH cells, co-expressing or not PD-1, ICOS, or CXCR3 markers was significantly higher in pregnant women (PW) as compared with non-pregnant ones (nPW). Furthermore, the percentage of CXCR3(+) TFH cells able to produce IL-6, IL-21, and IL-10 was significantly higher in PW than nPW...
April 27, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28479601/b7-dc-pd-l2-costimulation-of-cd4-t-helper-1-response-via-rgmb
#14
Xinxin Nie, Wenni Chen, Ying Zhu, Baozhu Huang, Weiwei Yu, Zhanshuai Wu, Sizheng Guo, Yiping Zhu, Liqun Luo, Shengdian Wang, Lieping Chen
The role of B7-DC in T-cell responses remains controversial because both coinhibitory and costimulatory functions have been reported in various experimental systems in vitro and in vivo. In addition to interacting with the coinhibitory receptor PD-1, B7-DC has also been shown to bind repulsive guidance molecule b (RGMb). The functional consequences of the B7-DC/RGMb interaction, however, remain unclear. More than a decade ago, we reported that replacement of a murine B7-DC mutant lysine with serine (K113S) at positive 113 resulted in a loss of binding capacity to PD-1...
May 8, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28475007/tim-3-plays-a-more-important-role-than-pd-1-in-the-functional-impairments-of-cytotoxic-t-cells-of-malignant-schwannomas
#15
Zhao Li, Xiaobing Liu, Rongbin Guo, Pengfei Wang
Cancer immunotherapy using cytotoxic T cells demonstrates dramatic survival benefits in lymphomas, but its efficacy in solid tumors is limited. Here, we investigated the possibility of using cytotoxic T cells to treat malignant Schwannoma, a rare but aggressive nerve sheath tumor, by examining the native T-cell immunity in the host. We found that compared to CD8(+) T cells from healthy controls or benign Schwannoma patients, the CD8(+) T cells from malignant Schwannoma patients were present at normal frequencies but were substantially enriched with PD-1(-)TIM-3(+) and PD-1(+)TIM-3(+) cells...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28473831/il-7-and-cd4-t-follicular-helper-cells-in-hiv-1-infection
#16
Francesca Chiodi, Yonas Bekele, Rebecka Lantto Graham, Aikaterini Nasi
IL-7 was previously shown to upregulate the expression of molecules important for interaction of CD4+ T cells with B cells. It is poorly studied whether IL-7 has a role in the biology of T follicular helper (Tfh) cells and whether IL-7 dysregulates the expression of B-cell costimulatory molecules on Tfh cells. We review the literature and provide arguments in favor of IL-7 being involved in the biology of human Tfh cells. The CD127 IL-7 receptor is expressed on circulating Tfh and non-Tfh cells, and we show that IL-7, but not IL-6 or IL-21, upregulates the expression of CD70 and PD-1 on these cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28469081/c3d-regulates-immune-checkpoint-blockade-and-enhances-antitumor-immunity
#17
Jeffrey L Platt, Inês Silva, Samuel J Balin, Adam R Lefferts, Evan Farkash, Ted M Ross, Michael C Carroll, Marilia Cascalho
Despite expression of immunogenic polypeptides, tumors escape immune surveillance by engaging T cell checkpoint regulators and expanding Tregs, among other mechanisms. What orchestrates these controls is unknown. We report that free C3d, a fragment of the third component of complement, inside tumor cells - or associated with irradiated tumor cells and unattached to antigen - recruits, accelerates, and amplifies antitumor T cell responses, allowing immunity to reverse or even to prevent tumor growth. C3d enhances antitumor immunity independently of B cells, NK cells, or antibodies, but it does so by increasing tumor infiltrating CD8+ lymphocytes, by depleting Tregs, and by suppressing expression of programmed cell death protein 1 (PD-1) by T cells...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28467522/eruptive-keratoacanthomas-associated-with-pembrolizumab-therapy
#18
Azael Freites-Martinez, Bernice Y Kwong, Kerri E Rieger, Daniel G Coit, A Dimitrios Colevas, Mario E Lacouture
Importance: To our knowledge, there have been no previous reports of eruptive keratoacanthomas (KAs) in patients receiving pembrolizumab. Objective: To report the cases of 3 consecutive patients with pembrolizumab-induced eruptive KAs and their management. Design, Setting, and Participants: Case report study of 3 patients from 2 centers with pembrolizumab-treated cancer who all developed eruptive KAs. Interventions: All 3 patients had AK treatment with clobetasol ointment and intralesional triamcinolone; 2 patients also underwent open superficial cryosurgery...
May 3, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28466250/outcomes-targeting-the-pd-1-pd-l1-axis-in-conjunction-with-stereotactic-radiation-for-patients-with-non-small-cell-lung-cancer-brain-metastases
#19
Kamran A Ahmed, Sungjune Kim, John Arrington, Arash O Naghavi, Thomas J Dilling, Ben C Creelan, Scott J Antonia, Jimmy J Caudell, Louis B Harrison, Solmaz Sahebjam, Jhanelle E Gray, Arnold B Etame, Peter A Johnstone, Michael Yu, Bradford A Perez
Anti-PD-1/PD-L1 therapies have demonstrated activity in patients with advanced stage non-small cell lung cancer (NSCLC). However, little is known about the safety and feasibility of patients receiving anti-PD-1/PD-L1 therapy and stereotactic radiation for the treatment of brain metastases. Data were analyzed retrospectively from NSCLC patients treated with stereotactic radiation either before, during or after anti-PD-1/PD-L1 therapy with nivolumab (anti-PD-1) or durvalumab (anti-PD-L1). Seventeen patients treated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiation therapy (FSRT) to 49 brain metastases over 21 sessions were identified...
May 2, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28463977/production-of-igg-antibodies-to-pneumococcal-polysaccharides-is-associated-with-expansion-of-icos-circulating-memory-t-follicular-helper-cells-which-is-impaired-by-hiv-infection
#20
Laila N Abudulai, Sonia Fernandez, Karli Corscadden, Sally A Burrows, Michael Hunter, M Christian Tjiam, Lea-Ann S Kirkham, Jeffrey J Post, Martyn A French
Dysfunction of T follicular-helper (TFH) cells is a possible cause of impaired germinal centre (GC) and IgG antibody responses in individuals with human immunodeficiency virus-1 (HIV-1) infection and might contribute to decreased magnitude and isotype diversification of IgG antibodies to pneumococcal polysaccharides (PcPs). We examined the production of IgG1 and IgG2 antibodies to PcPs 4, 6B, 9V and 14 by enumerating antibody secreting cells (ASCs) at day (D) 7 and determining fold-increase in serum antibody levels at D28 after vaccination with unconjugated PcPs in HIV seronegative subjects (n = 20) and in HIV patients who were receiving antiretroviral therapy (ART) (n = 28) or who were ART-naive (n = 11) and determined their association with ICOS+ and ICOS- circulating memory TFH (cmTFH) cells (CD4+CD45RA-CD27+CXCR5+PD-1+) and short lived plasmablasts (SPBs) at D7, and with PcP-specific and total IgM+ and IgG+ memory B cells at D0...
2017: PloS One
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