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PD-1 immune

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https://www.readbyqxmd.com/read/29779086/retrospective-study-of-nivolumab-for-patients-with-recurrent-high-grade-gliomas
#1
Megan Mantica, Ashley Pritchard, Frank Lieberman, Jan Drappatz
INTRODUCTION: Patients with recurrent high-grade gliomas (HGG) have limited treatment options. HGG utilize the PD-1 pathway to evade immune responses. Checkpoint inhibitors have demonstrated safety and clinical activity in patients with recurrent glioblastoma. We explored the efficacy of nivolumab in recurrent HGG with a primary objective of progression free survival (PFS) and overall survival (OS). METHODS: We retrospectively analyzed HGG patients treated with nivolumab in our institution...
May 19, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29778737/cancer-immunotherapy-efficacy-and-patients-sex-a-systematic-review-and-meta-analysis
#2
Fabio Conforti, Laura Pala, Vincenzo Bagnardi, Tommaso De Pas, Marco Martinetti, Giuseppe Viale, Richard D Gelber, Aron Goldhirsch
BACKGROUND: Despite the acknowledged sex-related dimorphism in immune system response, little is known about the effect of patients' sex on the efficacy of immune checkpoint inhibitors as cancer treatments. We did a systematic review and meta-analysis to assess the heterogeneity of immune checkpoint inhibitor efficacy between men and women. METHODS: We systematically searched PubMed, MEDLINE, Embase, and Scopus, from database inception to Nov 30, 2017, for randomised controlled trials of immune checkpoint inhibitors (inhibitors of PD-1, CTLA-4, or both) that had available hazard ratios (HRs) for death according to patients' sex...
May 16, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29776424/impaired-cd8-t-cell-antiviral-immunity-following-acute-spinal-cord-injury
#3
Diana M Norden, John R Bethea, Jiu Jiang
BACKGROUND: Spinal cord injury (SCI) disrupts essential neuroimmune communication, leading to severe immune depression. Previous studies confirmed immune dysfunction in mice with chronic SCI and following high thoracic level injury where sympathetic innervation of the spleen is disrupted. Here, we induced a mid-thoracic injury where integrity of the sympathetic response is maintained and investigated the antiviral T cell response to influenza virus after acute SCI. METHODS: One week following a contusion SCI at thoracic level T9, mice were infected intranasally with influenza virus...
May 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29775807/fir-efficacy-safety-and-biomarker-analysis-of-a-phase-ii-open-label-study-of-atezolizumab-in-pd-l1-selected-patients-with-non-small-cell-lung-cancer
#4
David R Spigel, Jamie E Chaft, Scott Gettinger, Bo H Chao, Luc Dirix, Peter Schmid, Laura Q M Chow, Rodney J Hicks, Larry Leon, Jill Fredrickson, Marcin Kowanetz, Alan Sandler, Roel Funke, Naiyer A Rizvi
INTRODUCTION: The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. METHODS: Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases)...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#5
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29773326/tremelimumab-combined-with-durvalumab-in-patients-with-mesothelioma-nibit-meso-1-an-open-label-non-randomised-phase-2-study
#6
Luana Calabrò, Aldo Morra, Diana Giannarelli, Giovanni Amato, Armida D'Incecco, Alessia Covre, Arthur Lewis, Marlon C Rebelatto, Riccardo Danielli, Maresa Altomonte, Anna Maria Di Giacomo, Michele Maio
BACKGROUND: Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study. We aimed to investigate the efficacy and safety of first-line or second-line tremelimumab combined with durvalumab, an anti-PD-L1 monoclonal antibody, in patients with malignant mesothelioma. METHODS: In this open-label, non-randomised, phase 2 trial, patients with unresectable pleural or peritoneal mesothelioma received intravenous tremelimumab (1 mg/kg bodyweight) and durvalumab (20 mg/kg bodyweight) every 4 weeks for four doses, followed by maintenance intravenous durvalumab at the same dose and schedule for nine doses...
May 14, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#7
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29769383/incidence-of-thyroid-function-test-abnormalities-in-patients-receiving-immune-checkpoint-inhibitors-for-cancer-treatment
#8
Nisha Subhash Patel, Anais Oury, Gregory A Daniels, Lyudmila Bazhenova, Sandip Pravin Patel
BACKGROUND: With the advent of immune-checkpoint inhibitor (ICI) therapy (anti-CTLA-4, anti-PD-1), immune-related adverse events such as thyroid function test abnormalities (TFTAs) are common, with a reported incidence range of 2%-15% depending upon the ICI used. The aim of this study is to describe the incidence of TFTAs retrospectively in patients who received ICI therapy. METHODS: A total of 285 patients were reviewed (178 male, 107 female; 16-94 years of age), of whom 218 had no baseline TFTAs, 61 had baseline TFTAs, and 6 had a history of thyroidectomy (excluded)...
May 16, 2018: Oncologist
https://www.readbyqxmd.com/read/29769249/spatial-distribution-and-function-of-t-follicular-regulatory-cells-in-human-lymph-nodes
#9
Ismail Sayin, Andrea J Radtke, Laura A Vella, Wenjie Jin, E John Wherry, Marcus Buggert, Michael R Betts, Ramin S Herati, Ronald N Germain, David H Canaday
T follicular regulatory (Tfr) cells are a population of CD4+ T cells that express regulatory T cell markers and have been shown to suppress humoral immunity. However, the precise mechanisms and location of Tfr-mediated suppression in the lymph node (LN) microenvironment are unknown. Using highly multiplexed quantitative imaging and functional assays, we examined the spatial distribution, suppressive function, and preferred interacting partners of Tfr cells in human mesenteric LNs. We find that the majority of Tfr cells express low levels of PD-1 and reside at the border between the T cell zone and B cell follicle, with very few found in the germinal centers (GCs)...
May 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29769148/current-landscape-and-future-of-dual-anti-ctla4-and-pd-1-pd-l1-blockade-immunotherapy-in-cancer-lessons-learned-from-clinical-trials-with-melanoma-and-non-small-cell-lung-cancer-nsclc
#10
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcelo R Cruz, Sunandana Chandra, Jaehyuk Choi, Francis Giles
Immunotherapy is among the most rapidly evolving treatment strategies in oncology. The therapeutic potential of immune-checkpoint inhibitors is exemplified by the recent hail of Food and Drug Administration (FDA) approvals for their use in various malignancies. Continued efforts to enhance outcomes with immunotherapy agents have led to the formulation of advanced treatment strategies. Recent evidence from pre-clinical studies evaluating immune-checkpoint inhibitors in various cancer cell-lines has suggested that combinatorial approaches may have superior survival outcomes compared to single-agent immunotherapy regimens...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29768369/pembrolizumab-induced-acute-thrombosis-a-case-report
#11
Kei Kunimasa, Kazumi Nishino, Madoka Kimura, Takako Inoue, Motohiro Tamiya, Toru Kumagai, Fumio Imamura
RATIONALE: Acute thrombosis has not been reported in the literature so far in lung cancer patients as an immune-related adverse event (irAE) associated with PD-1 pathway inhibitors. PATIENTS CONCERNS: Here, we for the first time present two NSCLC (non-small cell lung cancer) patients suffering from acute thrombosis as a pembrolizumab-induced irAE. Immediate treatment with continuous heparin infusion improved their symptoms and enabled them to continue pembrolizumab administration...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29765155/genetic-transcriptional-and-post-translational-regulation-of-the-programmed-death-protein-ligand-1-in-cancer-biology-and-clinical-correlations
#12
REVIEW
Ioannis Zerdes, Alexios Matikas, Jonas Bergh, George Z Rassidakis, Theodoros Foukakis
The programmed death protein 1 (PD-1) and its ligand (PD-L1) represent a well-characterized immune checkpoint in cancer, effectively targeted by monoclonal antibodies that are approved for routine clinical use. The regulation of PD-L1 expression is complex, varies between different tumor types and occurs at the genetic, transcriptional and post-transcriptional levels. Copy number alterations of PD-L1 locus have been reported with varying frequency in several tumor types. At the transcriptional level, a number of transcriptional factors seem to regulate PD-L1 expression including HIF-1, STAT3, NF-κΒ, and AP-1...
May 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29764856/-tp53-stk11-and-egfr-mutations-predict-tumor-immune-profile-and-the-response-to-anti-pd-1-in-lung-adenocarcinoma
#13
Jerome Biton, Audrey Mansuet-Lupo, Nicolas Pécuchet, Marco Alifano, Hanane Ouakrim, Jennifer Arrondeau, Pascaline Boudou-Rouquette, Francois Goldwasser, Karen Leroy, Jeremy Goc, Marie Wislez, Claire Germain, Pierre Laurent-Puig, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Ronald Herbst, Hélène F Blons, Diane Damotte
PURPOSE: By unlocking anti-tumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed. EXPERIMENTAL DESIGN: We performed in depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry and transcriptomic data...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29762727/development-of-targeted-therapy-and-immunotherapy-for-treatment-of-small-cell-lung-cancer
#14
Motonobu Saito, Kouya Shiraishi, Akiteru Goto, Hiroyuki Suzuki, Takashi Kohno, Koji Kono
Targeted therapy against druggable genetic aberrations has shown a significantly positive response rate and longer survival in various cancers, including lung cancer. In lung adenocarcinoma (LADC), specific thyroxin kinase inhibitors against EGFR mutations and ALK fusions are used as a standard treatment regimen and show significant positive efficacy. On the other hand, targeted therapy against driver gene aberrations has not been adapted yet in small cell lung cancer (SCLC). This is because driver genes and druggable aberrations are rarely identified by next generation sequencing in SCLC...
May 14, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29762141/pd-1-expression-in-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-cll-sll-and-large-b-cell-richter-transformation-dlbcl-rt-a-characteristic-feature-of-dlbcl-rt-and-potential-surrogate-marker-for-clonal-relatedness
#15
Rong He, Wei Ding, David S Viswanatha, Dong Chen, Min Shi, Daniel Van Dyke, Shulan Tian, Linda N Dao, Sameer A Parikh, Tait D Shanafelt, Timothy G Call, Stephen M Ansell, Jose F Leis, Ming Mai, Curtis A Hanson, Karen L Rech
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT...
May 14, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29760800/risk-of-immune-related-colitis-with-pd-1-pd-l1-inhibitors-vs-chemotherapy-in-solid-tumors-systems-assessment
#16
Qiang Su, Xiaochen Zhang, Xinhua Shen, Yanli Hou, Zhigang Sun, Zu Hua Gao
Background: We performed a meta-analysis to evaluate the risk of immune-related colitis associated with PD1/PD-L1 inhibitors as compared to chemotherapy in solid tumor patients. Methods: Eligible studies were identified through a comprehensive search of multiple databases and included solid tumor patients in randomized controlled trials (RCTs) with PD-1/PD-L1 inhibitors. The data was analyzed by Stata version 12.0 software. Results: After exclusion of ineligible studies, 11 clinical trials were considered eligible for the meta-analysis, including 5751 patients...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29760706/complement-opsonized-hiv-1-alters-cross-talk-between-dendritic-cells-and-natural-killer-nk-cells-to-inhibit-nk-killing-and-to-upregulate-pd-1-cxcr3-and-ccr4-on-t-cells
#17
Rada Ellegård, Mohammad Khalid, Cecilia Svanberg, Hanna Holgersson, Ylva Thorén, Mirja Karolina Wittgren, Jorma Hinkula, Sofia Nyström, Esaki M Shankar, Marie Larsson
Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760523/combination-of-fucoidan-based-magnetic-nanoparticles-and-immunomodulators-enhances-tumour-localized-immunotherapy
#18
Chih-Sheng Chiang, Yu-Jung Lin, Rachel Lee, Yen-Ho Lai, Hung-Wei Cheng, Chia-Hung Hsieh, Woei-Cherng Shyu, San-Yuan Chen
Checkpoint immunotherapy that inhibits tumour immune evasion has demonstrated significant clinical success. However, the therapeutic response is limited to certain patient populations, and immunotoxicity as well as autoimmunity have compromised the therapeutic benefits. Here, we report on an inherently therapeutic fucoidan-dextran-based magnetic nanomedicine (IO@FuDex3 ) conjugated with a checkpoint inhibitor (anti-PD-L1) and T-cell activators (anti-CD3 and anti-CD28). IO@FuDex3 can repair the immunosuppressive tumour microenvironment by reinvigorating tumour-infiltrating lymphocytes, while targeting the nanomedicine via magnetic navigation to the tumour to minimize off-target effects...
May 14, 2018: Nature Nanotechnology
https://www.readbyqxmd.com/read/29760383/outlier-response-to-anti-pd1-in-uveal-melanoma-reveals-germline-mbd4-mutations-in-hypermutated-tumors
#19
Manuel Rodrigues, Lenha Mobuchon, Alexandre Houy, Alice Fiévet, Sophie Gardrat, Raymond L Barnhill, Tatiana Popova, Vincent Servois, Aurore Rampanou, Aurore Mouton, Stéphane Dayot, Virginie Raynal, Michèle Galut, Marc Putterman, Sarah Tick, Nathalie Cassoux, Sergio Roman-Roman, François-Clément Bidard, Olivier Lantz, Pascale Mariani, Sophie Piperno-Neumann, Marc-Henri Stern
Metastatic uveal melanoma is a deadly disease with no proven standard of care. Here we present a metastatic uveal melanoma patient with an exceptional high sensitivity to a PD-1 inhibitor associated with outlier CpG>TpG mutation burden, MBD4 germline deleterious mutation, and somatic MBD4 inactivation in the tumor. We identify additional tumors in The Cancer Genome Atlas (TCGA) cohorts with similar hypermutator profiles in patients carrying germline deleterious MBD4 mutations and somatic loss of heterozygosity...
May 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29759483/induction-of-the-immunoproteasome-subunit-lmp7-links-proteostasis-and-immunity-in-%C3%AE-synuclein-aggregation-disorders
#20
Scott Ugras, Malcolm J Daniels, Hossein Fazelinia, Neal S Gould, Anastasia K Yocum, Kelvin C Luk, Esteban Luna, Hua Ding, Chris McKennan, Steven Seeholzer, Dan Martinez, Perry Evans, Daniel Brown, John E Duda, Harry Ischiropoulos
Accumulation of aggregated α-synuclein into Lewy bodies is thought to contribute to the onset and progression of dopaminergic neuron degeneration in Parkinson's disease (PD) and related disorders. Although protein aggregation is associated with perturbation of proteostasis, how α-synuclein aggregation affects the brain proteome and signaling remains uncertain. In a mouse model of α-synuclein aggregation, 6% of 6215 proteins and 1.6% of 8183 phosphopeptides changed in abundance, indicating conservation of proteostasis and phosphorylation signaling...
May 11, 2018: EBioMedicine
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