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PD-1 immune

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https://www.readbyqxmd.com/read/29333980/percentages-of-pd-1-cd4-t-cells-and-pd-l1-dcs-are-increased-and-spd-1-level-is-elevated-in-patients-with-immune-thrombocytopenia
#1
Yingying Wang, Nannan Pang, Xinyou Wang, Ying Liu, Xiujuan Wang, Lei Wang, Mingling Sun, Halida Yasen, Fang Zhao, Wenxia Fan, Jianbing Ding, Xinhong Guo
The present study is to measure the expression of programmed death (PD)-1 / programmed death ligand-1 (PD-L1) negative costimulatory molecules, soluble format sPD-1 in patients with immune thrombocytopenia (ITP), and to investigate their correlation with the secretion of cytokines. A total of 35 patients with ITP were included in the present study. Twenty healthy subjects who received physical examination at our hospital were included as control group. Peripheral blood was collected from all ITP patients and healthy subjects...
January 15, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29333023/nivolumab-pearls-of-evidence
#2
REVIEW
Pratishtha B Chaudhari
Purpose: Nivolumab is one of the most extensively studied immune checkpoint inhibitors across various tumor types. In this narrative review, the current clinical efficacy and safety data of anti-programmed death-1 (PD-1) nivolumab for nonsmall cell lung cancer (NSCLC) and renal cell cancer (RCC) are elucidated. Methods: Systematic search was done on Pubmed, Medline, Embase, Web of Knowledge, and Cochrane Central through September 2016 for controlled prospective interventional studies of nivolumab across two indications - NSCLC and RCC...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29332341/association-of-the-combined-parameters-including-the-frequency-of-primary-cilia-cd8-tumor-infiltrating-lymphocytes-and-pd-1-expression-with-the-outcome-in-intestinal-cancer
#3
Josef Dvorak, Dimitar Hadzi Nikolov, Ladislav Dusek, Alzbeta Filipova, Igor Richter, David Buka, Ales Ryska, Jaroslav Mokry, Stanislav Filip, Bohuslav Melichar, Tomas Buchler, Jitka Abrahamova
PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the immune synapse. Microtubule structures, PC of cancer associated fibroblasts and immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and cancer cells, are regularly found in varying amounts in the microenvironment of solid tumors. The purpose of this study was to find out the potential association and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331748/safety-and-efficacy-of-anti-programmed-death-1-antibodies-in-patients-with-cancer-and-pre-existing-autoimmune-or-inflammatory-disease
#4
François-Xavier Danlos, Anne-Laure Voisin, Valérie Dyevre, Jean-Marie Michot, Emilie Routier, Laurent Taillade, Stéphane Champiat, Sandrine Aspeslagh, Julien Haroche, Laurence Albiges, Christophe Massard, Nicolas Girard, Stéphane Dalle, Benjamin Besse, Salim Laghouati, Jean-Charles Soria, Christine Mateus, Caroline Robert, Emilie Lanoy, Aurélien Marabelle, Olivier Lambotte
OBJECTIVE: Patients with autoimmune or inflammatory disease (AID) are susceptible to immune-related adverse events (irAEs) when treated with immune check-point inhibitors (ICIs). We decided to analyse the safety and effectiveness of anti-PD-1 antibodies in AID patients and look for an association between the presence of pre-existing AID and the clinical outcome. METHODS: In a prospective study of the REISAMIC registry of grade ≥2 irAEs occurring in ICI-treated patients, we studied the associations between pre-existing AID on one hand and irAE-free survival, overall survival and best objective response rate on the other...
January 10, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#5
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ≥50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29330750/immunologic-and-gene-expression-profiles-of-spontaneous-canine-oligodendrogliomas
#6
Anna Filley, Mario Henriquez, Tanmoy Bhowmik, Brij Nath Tewari, Xi Rao, Jun Wan, Margaret A Miller, Yunlong Liu, R Timothy Bentley, Mahua Dey
Malignant glioma (MG), the most common primary brain tumor in adults, is extremely aggressive and uniformly fatal. Several treatment strategies have shown significant preclinical promise in murine models of glioma; however, none have produced meaningful clinical responses in human patients. We hypothesize that introduction of an additional preclinical animal model better approximating the complexity of human MG, particularly in interactions with host immune responses, will bridge the existing gap between these two stages of testing...
January 12, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29330579/-initially-undetected-de-novo-psoriasis-triggered-by-nivolumab-for-metastatic-base-of-the-tongue-carcinoma
#7
S Troyanova-Slavkova, L Eickenscheidt, K Dumann, L Kowalzick
Nivolumab is a monoclonal antibody that binds to the PD-1 receptor on T cells and inhibits the interaction with the PD-L1 and PD-L2 ligands on cancer cells. Thus, nivolumab has immunostimulatory properties. The known side effects of this therapy include fatigue, skin rash, dysfunction of the thyroid gland and colitis, which are explained by the immunoregulatory mechanisms of the drug. Here we report on the case of a 58-year-old man with metastatic base of tongue carcinoma who developed de novo psoriasis triggered by nivolumab...
January 12, 2018: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/29330552/dosimetry-prediction-for-clinical-translation-of-64cu-pembrolizumab-immunopet-targeting-human-pd-1-expression
#8
Arutselvan Natarajan, Chirag B Patel, Frezghi Habte, Sanjiv S Gambhir
The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#9
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29328976/pattern-of-programmed-cell-death-ligand-1-expression-and-cd8-positive-t-cell-infiltration-before-and-after-chemoradiotherapy-in-rectal-cancer
#10
Atsushi Ogura, Takashi Akiyoshi, Noriko Yamamoto, Hiroshi Kawachi, Yuichi Ishikawa, Seiichi Mori, Koji Oba, Masato Nagino, Yosuke Fukunaga, Masashi Ueno
BACKGROUND: The synergistic effect of combining immune checkpoint inhibitors with radiotherapy was reported recently, but there are few studies on programmed cell death-ligand 1 (PD-L1) expression in rectal cancer treated by preoperative chemoradiotherapy (CRT). The aim of the present study was to investigate the PD-L1 expression status before and after CRT and its association with clinicopathological characteristics and recurrence in rectal cancer. METHODS: Immunostainings of PD-L1 and CD8 were performed in 287 patients with rectal cancer treated by CRT...
January 9, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29328389/mir-375-inhibits-ifn-%C3%AE-induced-programmed-death-1-ligand%C3%A2-1-surface-expression-in-head-and-neck-squamous-cell-carcinoma-cells-by-blocking-jak2-stat1-signaling
#11
Qingwei Wu, Yingying Zhao, Yiyuan Sun, Xiaojun Yan, Peihua Wang
Upregulation of programmed death 1 ligand 1 (PD-L1) in cancer cells and its ligation to PD-1 on T cells facilitates cancer cell escape from immune surveillance. Therapies with PD-1 or PD-L1 antibodies have resulted in marked clinical responses in various cancer types. Hence, modulators that inhibit PD-L1 expression in cancer cells may serve as a novel strategy by which to enhance host immune responses. In the present study, we investigated the effects of miR-375 on PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) cells by qRT-PCR and western blot analyses...
January 2, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29327044/association-of-the-lung-immune-prognostic-index-with-immune-checkpoint-inhibitor-outcomes-in-patients-with-advanced-non-small-cell-lung-cancer
#12
Laura Mezquita, Edouard Auclin, Roberto Ferrara, Melinda Charrier, Jordi Remon, David Planchard, Santiago Ponce, Luis Paz Ares, Laura Leroy, Clarisse Audigier-Valette, Enriqueta Felip, Jorge Zerón-Medina, Pilar Garrido, Solenn Brosseau, Gérard Zalcman, Julien Mazieres, Caroline Caramela, Jihene Lahmar, Julien Adam, Nathalie Chaput, Jean Charles Soria, Benjamin Besse
Importance: Derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitor (ICI) outcomes in patients with melanoma. Objective: To determine whether pretreatment dNLR and LDH are associated with resistance to ICIs in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: Multicenter retrospective study with a test (n = 161) and a validation set (n = 305) treated with programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors in 8 European centers, and a control cohort (n = 162) treated with chemotherapy only...
January 11, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29326088/age-effects-of-distinct-immune-checkpoint-blockade-treatments-in-a-mouse-melanoma-model
#13
Álvaro Padrón, Vincent Hurez, Harshita B Gupta, Curtis A Clark, Sri Lakshmi Pandeswara, Bin Yuan, Robert S Svatek, Mary Jo Turk, Justin M Drerup, Rong Li, Tyler J Curiel
Cancer immunotherapy has shown remarkable recent progress. Immune checkpoint blocking antibodies have become the most successful anti-cancer agent class ever developed, with six distinct agents approved since 2011 for a wide variety of cancers. Although age is the biggest risk factor for cancer (aside from selected early-onset pediatric cancers), these agents were tested pre-clinically in young hosts, and there is remarkably little published on the effects of host age on treatment outcomes in pre-clinical studies or human clinical trials...
January 8, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29326017/small-molecule-immuno-oncology-therapeutic-agents
#14
REVIEW
Peter L Toogood
Treatment of cancer by activation of an antitumor immune response is now a widely practiced and well-accepted approach to therapy. However, despite dramatic responses in some patients, the high proportion of unresponsive patients points to a considerable unmet medical need. Although antibody therapies have led the way, small molecule immuno-oncology agents are close behind. This perspective provides an overview of some of the many small molecule approaches being explored. It encompasses small molecule modulators of validated targets such as programed cell death 1 (PD-1) as well as novel approaches still to be proven clinically...
December 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29325739/anti-programmed-cell-death-1-ligand-1-pd-1-pd-l1-antibodies-for-the-treatment-of-urothelial-carcinoma-state-of-the-art-and-future-development
#15
REVIEW
Thomas Powles, Andrea Necchi, Galit Rosen, Subramanian Hariharan, Andrea B Apolo
Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint inhibitors has expanded a previously limited pool of effective treatment options for patients with metastatic urothelial carcinoma, particularly those with recurring or refractory disease and those who are ineligible for cisplatin. This review reports key findings from completed and ongoing clinical trials that highlight the potential of PD-1/PD-L1 blockade in urothelial carcinoma. A literature search was performed of PubMed, Embase, ClinicalTrials...
December 6, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29325434/collection-of-real-world-data-on-nivolumab-s-effectiveness-in-renal-cell-carcinoma-rationale-for-an-observational-study
#16
Jens Bedke, Marc-Oliver Grimm, Viktor Grünwald
Renal cell carcinoma (RCC) represents the seventh (men) respectively tenth (women) most frequent cancer in western countries. After one or more lines of VEGF-targeted therapy, immunotherapy with nivolumab is strongly recommended in patients with metastatic RCC. Nivolumab is the first, and so far, only approved programmed death 1 (PD-1) immune checkpoint inhibitor to demonstrate a gain in overall survival in RCC. We describe herein design and rationale of trial CA209653 ('NIS NORA'), a prospective, noninterventional cohort study investigating the effectiveness of nivolumab...
January 12, 2018: Future Oncology
https://www.readbyqxmd.com/read/29322496/wt1-peptide-based-immunotherapy-for-advanced-thymic-epithelial-malignancies
#17
Yusuke Oji, Masayoshi Inoue, Yoshito Takeda, Naoki Hosen, Yasushi Shintani, Manabu Kawakami, Takuya Harada, Yui Murakami, Miki Iwai, Mari Fukuda, Sumiyuki Nishida, Jun Nakata, Yoshiki Nakae, Satoshi Takashima, Toshiaki Shirakata, Hiroko Nakajima, Kana Hasegawa, Hiroshi Kida, Takashi Kijima, Soyoko Morimoto, Fumihiro Fujiki, Akihiro Tsuboi, Eiichi Morii, Satoshi Morita, Junichi Sakamoto, Atsushi Kumanogoh, Yoshihiro Oka, Meinoshin Okumura, Haruo Sugiyama
Thymic epithelial tumors are rare malignancies, and no optimal therapeutic regimen has been defined for patients with advanced disease. Patients with advanced thymic epithelial tumors, which were resistant or intolerable to prior therapies, were eligible for this study. Patients received 9 mer-WT1-derived peptide emulsified with Montanide ISA51 adjuvant via intradermal administration once a week as a monotherapy. After the 3 month-protocol treatment, the treatment was continued mostly at intervals of 2 to 4 weeks until disease progression or intolerable adverse events occurred...
January 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29322203/program-death-inhibitors-in-classical-hodgkin-s-lymphoma-a-comprehensive-review
#18
REVIEW
Reyad Dada
Cancer cells are able to induce immune system tolerance through different mechanisms. Recent achievements in the understanding of tumor microenvironment, invasion, and metastasizing have contributed to accelerated drug developments and approvals. Hodgkin lymphoma (HL) cells are the minority in a lymphocyte-rich microenvironment of HL tissue. The program death-1 (PD-1)/PD-ligand-1 checkpoint is one of the known effective pathways in classical HL to escape the immune system cells. The approval of PD-1 inhibitors in different cancer types with exciting response rates is truly revolutionizing our treatment armamentarium against cancer in general and classical HL in specific...
January 10, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29320474/high-response-rate-to-pd-1-blockade-in-desmoplastic-melanomas
#19
Zeynep Eroglu, Jesse M Zaretsky, Siwen Hu-Lieskovan, Dae Won Kim, Alain Algazi, Douglas B Johnson, Elizabeth Liniker, Ben Kong, Rodrigo Munhoz, Suthee Rapisuwon, Pier Federico Gherardini, Bartosz Chmielowski, Xiaoyan Wang, I Peter Shintaku, Cody Wei, Jeffrey A Sosman, Richard W Joseph, Michael A Postow, Matteo S Carlino, Wen-Jen Hwu, Richard A Scolyer, Jane Messina, Alistair J Cochran, Georgina V Long, Antoni Ribas
Desmoplastic melanoma is a rare subtype of melanoma characterized by dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations, and is highly associated with ultraviolet light-induced DNA damage. We analysed sixty patients with advanced desmoplastic melanoma who had been treated with antibodies to block programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1). Objective tumour responses were observed in forty-two of the sixty patients (70%; 95% confidence interval 57-81%), including nineteen patients (32%) with a complete response...
January 10, 2018: Nature
https://www.readbyqxmd.com/read/29319621/selective-cd28-inhibition-modulates-alloimmunity-and-cardiac-allograft-vasculopathy-in-anti-cd154-treated-monkeys
#20
Tianshu Zhang, Agnes M Azimzadeh, Wenji Sun, Natalie A O'Neill, Evelyn Sievert, Emily Bergbower, Gheorghe Braileanu, Lars Burdorf, Xiangfei Cheng, Thomas Monahan, Siamak Dahi, Donald Harris, Elana Rybak, Emily Welty, Anthony Kronfli, Chris Avon, Richard N Pierson
BACKGROUND: Selective CD28 inhibition is actively pursued as an alternative to B7 blockade using CTLA4-Ig based on the hypothesis that the checkpoint immune regulators CTLA-4 and PD-L1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single chain anti-CD28 Fv fragment linked to alpha-1 anti-trypsin: sc28AT) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week 'induction" sc28AT treatment with prolonged CD154 blockade...
January 10, 2018: Transplantation
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