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https://www.readbyqxmd.com/read/29221649/-two-cases-of-granuloma-annulare-under-anti-pd1-therapy
#1
R Charollais, F Aubin, B Roche-Kubler, E Puzenat
BACKGROUND: Granuloma annulare as a granulomatous cutaneous reaction may be drug-induced. Immune checkpoint inhibitors including programmed death-1 (PD-1) inhibitors show remarkable antitumor activity and are approved for melanoma and other cancers. Different immune-related adverse effects have been described. We report herein a rare adverse effect of anti-PD1 therapy given for metastatic melanoma : granuloma annulare. PATIENTS AND METHODS: Two women receiving pembrolizumab metastatic melanoma presented with granuloma annulare...
December 5, 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#2
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29217299/high-pd-l1-cd86-mfi-ratio-and-il-10-secretion-characterize-human-regulatory-dendritic-cells-generated-for-clinical-testing-in-organ-transplantation
#3
Alan F Zahorchak, Camila Macedo, David E Hamm, Lisa H Butterfield, Diana M Metes, Angus W Thomson
Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression...
September 14, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29217288/avelumab-in-metastatic-urothelial-carcinoma-after-platinum-failure-javelin-solid-tumor-pooled-results-from-two-expansion-cohorts-of-an-open-label-phase-1-trial
#4
Manish R Patel, John Ellerton, Jeffrey R Infante, Manish Agrawal, Michael Gordon, Raid Aljumaily, Carolyn D Britten, Luc Dirix, Keun-Wook Lee, Mathew Taylor, Patrick Schöffski, Ding Wang, Alain Ravaud, Arnold B Gelb, Junyuan Xiong, Galit Rosen, James L Gulley, Andrea B Apolo
BACKGROUND: The approval of anti-programmed death ligand 1 (PD-L1) and anti-programmed death 1 agents has expanded treatment options for patients with locally advanced or metastatic urothelial carcinoma. Avelumab, a human monoclonal anti-PD-L1 antibody, has shown promising antitumour activity and safety in this disease. We aimed to assess the safety profile in patients (both post-platinum therapy and cisplatin-naive) treated with avelumab and to assess antitumour activity of this drug in post-platinum patients...
December 4, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29211042/newly-emerging-immune-checkpoints-promises-for-future-cancer-therapy
#5
REVIEW
Robert J Torphy, Richard D Schulick, Yuwen Zhu
Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3), B and T lymphocyte attenuator (BTLA), programmed death-1 homolog (PD-1H), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3)/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), and the poliovirus receptor (PVR)-like receptors...
December 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29209918/molecular-classification-and-precision-therapy-of-cancer-immune-checkpoint-inhibitors
#6
Yingyan Yu
On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers...
December 5, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/29209522/immune-checkpoint-inhibitors-for-advanced-non-small-cell-lung-cancer-emerging-sequencing-for-new-treatment-targets
#7
REVIEW
Pedro Nazareth Aguiar, Ramon Andrade De Mello, Carmelia Maria Noia Barreto, Luke Alastair Perry, Jahan Penny-Dimri, Hakaru Tadokoro, Gilberto de Lima Lopes
Lung cancer is the leading cause of cancer-related deaths in the world. Immune checkpoint inhibitors (ICI) stimulate cytotoxic lymphocyte activity against tumour cells. These agents are available for the treatment of non-small cell lung cancer (NSCLC) after failure of platinum-based therapy. One recent study has demonstrated that ICI monotherapy was superior to platinum-based chemotherapy for first-line treatment. Nevertheless, this benefit was only for a minority of the population (30%) whose tumour programmed death receptor ligand-1 (PD-L1) expression was above 50%...
2017: ESMO Open
https://www.readbyqxmd.com/read/29208908/multiplex-three-dimensional-optical-mapping-of-tumor-immune-microenvironment
#8
Steve Seung-Young Lee, Vytautas P Bindokas, Stephen J Kron
Recent developments in optical tissue clearing and microscopic imaging have advanced three-dimensional (3D) visualization of intact tissues and organs at high resolution. However, to expand applications to oncology, critical limitations of current methods must be addressed. Here we describe transparent tissue tomography (T3) as a tool for rapid, three-dimensional, multiplexed immunofluorescent tumor imaging. Cutting tumors into sub-millimeter macrosections enables simple and rapid immunofluorescence staining, optical clearing, and confocal microscope imaging...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29207936/fatal-graft-versus-host-disease-after-allogeneic-stem-cell-transplantation-in-a-patient-recently-exposed-to-nivolumab
#9
Ana Jiménez-Ubieto, Antonia Rodriguez, Pilar Martinez Sánchez, Adolfo Gómez, Yolanda Rodriguez, Gonzalo Carreño-Tarragona, Joaquín Martinez-López, Carlos Grande
Allogeneic hematopoietic stem cell transplantation and checkpoint blockade therapy are immune-based salvage therapies for Hodgkin's lymphoma; however, the use of programmed death 1 blocking agents in the allogeneic stem cell transplantation setting could augment the incidence of steroid refractory graft-versus-host disease. Few studies suggest that that nivolumab is safe in patients previously treated with an allogeneic stem cell transplantation. Likewise, there are very limited data on the use of nivolumab before allogeneic stem cell transplantation...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29206680/immune-therapies-in-acute-myeloid-leukemia-a-focus-on-monoclonal-antibodies-and-immune-checkpoint-inhibitors
#10
Rita Assi, Hagop Kantarjian, Farhad Ravandi, Naval Daver
PURPOSE OF REVIEW: This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). RECENT FINDINGS: The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML...
December 4, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29206673/pd-l1-expression-tumor-infiltrating-lymphocytes-and-clinical-outcome-in-patients-with-surgically-resected-esophageal-cancer
#11
Taisuke Yagi, Yoshifumi Baba, Takatsugu Ishimoto, Masaaki Iwatsuki, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Hideo Baba
OBJECTIVES: To examine the prognostic impact of the programmed death ligand 1 (PD-L1) expression, tumor-infiltrating lymphocyte (TIL) status, and their combination in esophageal cancer. SUMMARY BACKGROUND DATA: PD-L1 has garnered much attention for its roles in tumor immunology and as an immune-based therapeutic target. To ensure a response to PD-L1 checkpoint inhibitor, a new framework based on PD-L1 expression and the presence or absence of TILs is required. METHODS: Using a nonbiased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (cluster of differentiation 8 (CD8) expression) by immunohistochemical analysis...
December 4, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/29205636/immune-checkpoint-molecules-soluble-program-death-ligand-1-and-galectin-9-are-increased-in-pregnancy
#12
Elizabeth Ann L Enninga, Susan M Harrington, Douglas J Creedon, Rodrigo Ruano, Svetomir N Markovic, Haidong Dong, Roxana S Dronca
PROBLEM: Pregnancy requires balance between tolerance to the haploidentical fetus and the mother's ability to mount immune responses. There are parallels to this phenomenon that occur in metastatic cancer. We assessed soluble program death ligand-1 soluble PD-L1 (sPD-L1) and galectin-9 in the blood of pregnant women during gestation as these molecules are highly involved in immune suppression during cancer. METHOD OF STUDY: Maternal blood was collected from 30 primigravida women at monthly intervals during pregnancy, delivery and 6-week post-partum...
December 4, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29203283/understanding-the-structural-and-energetic-basis-of-pd-1-and-monoclonal-antibodies-bound-to-pd-l1-a-molecular-modeling-perspective
#13
Danfeng Shi, Shuangyan Zhou, Xuewei Liu, Chenxi Zhao, Huanxiang Liu, Xiaojun Yao
BACKGROUND: The inhibitors blocking the interaction between programmed cell death protein 1(PD-1) and programmed death-ligand 1(PD-L1) can activate the immune response of T cell and eliminate cancer cells. The crystallographic studies have provided structural insights of the interactive interfaces between PD-L1 and its protein ligands. However, the hotspot residues on PD-L1 as well as structural and energetic basis for different protein ligands still need to be further investigated. METHODS: Molecular modeling methods including molecular dynamics simulation, per-residue free energy decomposition, virtual alanine scanning mutagenesis and residue-residue contact analysis were used to qualitatively and quantitatively analyze the interactions between PD-L1 and different protein ligands...
December 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29202406/pyrano-3-2-a-carbazole-alkaloids-as-effective-agents-against-ischemic-stroke-in%C3%A2-vitro-and-in%C3%A2-vivo
#14
Yingda Zang, Xiuyun Song, Chuangjun Li, Jie Ma, Shifeng Chu, Dandan Liu, Qian Ren, Yan Li, Naihong Chen, Dongming Zhang
A series of pyrano[3,2-a]carbazole alkaloids were designed and synthesized as analogues of Claulansine F (Clau F, 10a) isolated from Clausena lansium. Some of compounds showed strong neuroprotective effects and were promising agents against ischemic stroke. Among these compounds, 7c was the most active in inhibiting the programmed death of PC12 cells and primary cortical neurons. This compound induced neuroprotection following ischemic reperfusion and decreased neurological deficit scores in treated animals...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29200165/programmed-death-ligand-1-expression-in-classical-hodgkin-lymphoma-in-pediatric-patients
#15
(no author information available yet)
No abstract text is available yet for this article.
December 1, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29200102/adult-primary-immune-thrombocytopenia-spleen-histology-findings-and-outcomes-according-to-rituximab-use-based-on-analysis-of-41-cases
#16
Adeline Furudoï, Étienne Rivière, Estibaliz Lazaro, Enio Furudoï, Jean-François Viallard, Marie Parrens
Immune thrombocytopenia (ITP) is an acquired antibody-mediated disease, for which splenectomy remains a curative treatment. We analyzed histology and phenotypes of ITP-splenectomy specimens from 41 adult patients, with different previous ITP-specific treatments, including B-cell-depleting rituximab (RTX) or not, in an attempt to predict splenectomy success or failure on the basis of day 56 postoperative platelet counts. RTX-naive ITP-spleen samples, compared with those from a 20-patient control trauma cohort, contained the following nonspecific, ITP-evocative, white-pulp lesions: follicular helper T-cell (programmed death-1 and inducible T-cell COStimulator) expansion in reactive follicles (P=0...
December 1, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29200081/pd-1-inhibitor-associated-myopathies-emerging-immune-mediated-myopathies
#17
Teerin Liewluck, Justin C Kao, Michelle L Mauermann
Programmed death-1 (PD-1) inhibitors are increasingly used in cancer immunotherapy. Various immune-related adverse events are reported, including infrequent individual case reports of myositis or rhabdomyolysis. The frequency and diagnostic spectrum of immune-related adverse events affecting skeletal muscle in PD-1 inhibitor-treated patients are unknown. We searched the Mayo Clinic Pharmacy database (2014-2016) to identify patients who developed myopathies during or after PD-1 inhibitor therapy. Among 654 cancer patients received PD-1 inhibitors (pembrolizumab=389; nivolumab=264; both=1), we identified 5 patients (pembrolizumab=5) with biopsy-proven myopathies (2 necrotizing myopathy, 1 early dermatomyositis, and 2 nonspecific myopathy)...
December 1, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29196189/pd-l1-inflammation-non-coding-rnas-and-neuroblastoma-immuno-oncology-perspective
#18
REVIEW
Palanisamy Nallasamy, Srinivas Chava, Sumit S Verma, Shruti Mishra, Santhi Gorantla, Don W Coulter, Siddappa N Byrareddy, Surinder K Batra, Subash C Gupta, Kishore B Challagundla
Neuroblastoma is the most common pediatric solid tumor of neural crest origin. The current treatment options for neuroblastoma produce severe side effects. Programmed death-ligand 1 (PD-L1), chronic inflammation, and non-coding RNAs are known to play a significant role in the pathogenesis of neuroblastoma. Cancer cells and the surrounding cells in the tumor microenvironment express PD-L1. Programmed death-1 (PD-1) is a co-receptor expressed predominantly by T cells. The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system...
November 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29195578/programmed-death-cell-ligand-1-pd-l1-is-associated-with-survival-in-stage-i-non-small-cell-lung-cancer
#19
Boris Sepesi, Edwin Parra Cuentas, Jaime Rodriguez Canales, Carmen Behrens, Arlene M Correa, Ara Vaporciyan, Annikka Weissferdt, Neda Kalhor, Cesar Moran, Stephen Swisher, Ignacio Wistuba
Programmed cell death ligand (PD-L1) has been studied as a predictive immunotherapy biomarker. We investigated PD-L1 expression in the whole tumor and in tumor-infiltrating macrophages (TIMs) as a prognostic biomarker in surgically resected pathologic stage I non-small cell lung cancer. Pathologic specimen from 113 patients with stage I lung cancer (pT1-2a, N0, M0, tumor size 1-5 cm, 79 adenocarcinoma, 34 squamous cell carcinoma) were analyzed for PD-L1 expression in the tumor and in the TIMs using immunohistochemistry and image analysis...
2017: Seminars in Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/29195503/recent-development-in-clinical-applications-of-pd-1-and-pd-l1-antibodies-for-cancer-immunotherapy
#20
REVIEW
Bingshan Liu, Yongping Song, Delong Liu
Antibodies against programmed death (PD) pathway are revolutionizing cancer immunotherapy. Currently five antibodies against PD-1/PD-L1 have been approved. The clinical use of these antibodies is rapidly expanding. Incorporation of PD antibodies into chemotherapy regimens is in active clinical investigations. The combination of pembrolizumab with carboplatin and pemetrexed has been approved for the first line therapy of metastatic non-squamous non-small cell lung cancer. Combination of PD-1/PD-L1 antibodies with small molecule inhibitors such as tyrosine kinase inhibitors and IDO inhibitors are in active clinical trials...
December 1, 2017: Journal of Hematology & Oncology
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