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Anti-PD1

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https://www.readbyqxmd.com/read/29351920/exceptional-response-to-pembrolizumab-in-a-metastatic-chemotherapy-radiation-resistant-ovarian-cancer-patient-harboring-a-cd274-pd-l1-genetic-rearrangement
#1
Stefania Bellone, Natalia Buza, Jungmin Choi, Luca Zammataro, Laurie Gay, Julia A Elvin, David L Rimm, Yuting Liu, Elena Ratner, Peter E Schwartz, Alessandro D Santin
PURPOSE: Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed. EXPERIMENTAL DESIGN: We describe a heavily pretreated ovarian cancer patient with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune check-point inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (ie, automated quantitative analysis, AQUA) and whole exome sequencing (WES) techniques...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-synergizes-with-anti-pd1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#2
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veerabhadran Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by tumor suppressor gene TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29339141/-immunotherapy-in-renal-cell-carcinoma-a-booming-clinical-research
#3
N Baize, P Bigot
CONTEXT: Nivolumab, an anti-PD1 immune control point inhibitor, is the first treatment that has improved the overall survival of patients after first-line metastatic renal cell carcinoma in 2015. Over the past two years, a large number of trials on these treatments and the interest of associations are being evaluated. OBJECTIVE: In this article, we propose to summarize the clinical development of checkpoint inhibitors to assess the direction of clinical research in this area...
January 12, 2018: Progrès en Urologie
https://www.readbyqxmd.com/read/29337311/dinaciclib-induces-immunogenic-cell-death-and-enhances-anti-pd-1-mediated-tumor-suppression
#4
Dewan Md Sakib Hossain, Sarah Javaid, Mingmei Cai, Chunsheng Zhang, Anandi Sawant, Marlene Hinton, Manjiri Sathe, Jeff Grein, Wendy Blumenschein, Elaine M Pinheiro, Alissa Chackerian
Blockade of the checkpoint inhibitor programmed death 1 (PD1) has demonstrated remarkable success in the clinic for the treatment of cancer; however, a majority of tumors are resistant to anti-PD1 monotherapy. Numerous ongoing clinical combination therapy studies will likely reveal additional therapeutics that complement anti-PD1 blockade. Recent studies found that immunogenic cell death (ICD) improves T cell responses against different tumors, thus indicating that ICD may further augment antitumor immunity elicited by anti-PD1...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29336431/anti-pd1-in-the-wonder-gut-land
#5
Marie Vetizou, Giorgio Trinchieri
After the initial success of cancer immunotherapy using immune checkpoint blockers, the challenge is to understand why only a minority of patients respond to the therapy and to increase the rate of response. Three recent papers now report that the gut microbiota modulates the response to anti-PD1 therapy in patients with epithelial cancers or melanoma.
January 16, 2018: Cell Research
https://www.readbyqxmd.com/read/29327065/blood-predictive-biomarkers-for-nivolumab-in-advanced-melanoma
#6
Edouard Chasseuil, Mélanie Saint-Jean, Hannah Chasseuil, Lucie Peuvrel, Gaëlle Quéreux, Jean-Michel Nguyen, Aurélie Gaultier, Emilie Varey, Amir Khammari, Brigitte Dréno
Nivolumab response rate is 40% in metastatic melanoma. Few studies have evaluated pre-treatment biomarkers predictive of response. The aim of this study was to identify potential peripheral blood biomarkers associated with survival in patients with advanced melanoma treated with nivolumab. All advanced melanoma cases treated with anti-programmed cell death protein 1 (anti-PD1) over a 3-year period in our department were identified. For each case, 9 potential blood biomarkers were identified. Bivariate and multivariate analyses, adjusted for the American Joint Committee on Cancer (AJCC) classification stage, Eastern Cooperative Oncology Group (ECOG) performance status, lactate dehydrogenase (LDH) level and failure to respond to first-line therapy, were used to test the association between biomarkers and overall survival (primary outcome) or progression-free survival (secondary outcome)...
December 20, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29312678/why-anti-pd1-pdl1-therapy-is-so-effective-another-piece-in-the-puzzle
#7
EDITORIAL
Antonio Marchetti, Alessia Di Lorito, Fiamma Buttitta
No abstract text is available yet for this article.
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29312568/transcriptional-response-to-hypoxic-stress-in-melanoma-and-prognostic-potential-of-gbe1-and-bnip3
#8
Stéphanie Buart, Stéphane Terry, Muhammad Z Noman, Emilie Lanoy, Céline Boutros, Paul Fogel, Philippe Dessen, Guillaume Meurice, Yann Gaston-Mathé, Philippe Vielh, Séverine Roy, Emilie Routier, Virginie Marty, Sophie Ferlicot, Luc Legrès, Morad El Bouchtaoui, Nyam Kamsu-Kom, Jane Muret, Eric Deutsch, Alexander Eggermont, Jean-Charles Soria, Caroline Robert, Salem Chouaib
Gradients of hypoxia occur in most solid tumors and cells found in hypoxic regions are associated with the most aggressive and therapy-resistant fractions of the tumor. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia in melanoma. Using microarray technology, whole genome gene expression profiling was first performed on established melanoma cell lines. From gene set enrichment analyses, we derived a robust 35 probes signature (hypomel for HYPOxia MELanoma) associated with hypoxia-response pathways, including 26 genes up regulated, and 9 genes down regulated...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311234/mycoplasma-bovis-induced-inhibition-of-bovine-pbmc-proliferation-is-ameliorated-after-blocking-the-immune-inhibitory-programmed-death-1-pd-1-receptor
#9
Muhammad Suleman, Farhan S Cyprian, Steve Jimbo, Teresia Maina, Tracy Prysliak, Claire Windeyer, Jose Perez-Casal
Mycoplasma bovis (M. bovis) induced-immune suppression is a major obstacle faced by the host for controlling infections. M. bovis impairment of antigen-specific T-cells responses is achieved through inhibiting the proliferation of peripheral-blood mononuclear cells (PBMC). This impairment may contribute to the persistence of M. bovis infection in various sites including lungs and its systemic spread to various organs like joints, with the underlying mechanisms remaining elusive. Here, we elucidated the role of the immune-inhibitory receptor programmed death-1 (PD-1) and its ligand (PD-L1) in M...
January 8, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29303012/blockade-of-ccr5-mediated-myeloid-derived-suppressor-cell-accumulation-enhances-anti-pd1-efficacy-in-gastric-cancer
#10
Liu Yang, Bing Wang, Jian Qin, HengHua Zhou, Adhip P N Majumdar, Fei Peng
PURPOSE: Myeloid derived suppressor cells (MDSC) play an important role in tumor immune evasion and its level significantly increased in patients with gastric cancer. Studies confirmed the associations between MDSC and various cytokines in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and CCR5 level in gastric cancer. MATERIALS AND METHODS: G-MDSC and M-MDSC from the peripheral blood and tumor parenchyma were analyzed by flow cytometry...
January 5, 2018: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/29298730/cytokine-release-syndrome-after-radiation-therapy-case-report-and-review-of-the-literature
#11
Christopher A Barker, Samuel K Kim, Sadna Budhu, Konstantina Matsoukas, Anthony F Daniyan, Sandra P D'Angelo
BACKGROUND: Cytokine release syndrome (CRS) has been reported after immunologic manipulations, most often through therapeutic monoclonal antibodies. To our knowledge, CRS after radiation therapy (RT) for cancer has not been reported before. The development of unusual clinical signs and symptoms after RT led us to investigate the possibility of CRS after RT and review the medical literature on this topic. CASE PRESENTATION: A 65 year-old man with untreated chronic lymphocytic leukemia and recurrent, metastatic Merkel cell carcinoma undergoing anti-programmed death 1 (PD1) immunotherapy was referred for palliative RT to sites of progressing metastases...
January 3, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29289336/-hodgkin-lymphoma-current-and-future-therapeutic-strategies
#12
REVIEW
Anthony Turpin, Jean-Marie Michot, Emmanuelle Kempf, Renaud Mazeron, Peggy Dartigues, Angela Boros, Serge Bonnetier, Cristina Castilla-Llorente, Tereza Coman, Alina Danu, David Ghez, Sylvain Pilorge, Julia Arfi-Rouche, Laurent Dercle, Jean-Charles Soria, Patrice Carde, Vincent Ribrag, Christophe Fermé, Julien Lazarovici
Hodgkin lymphoma (HL) is a cancer that mostly affects young people, in which modern therapeutic strategies using chemotherapy and radiotherapy result in a cure rate exceeding 80%. Survivors are exposed to long-term consequences of treatments, such as secondary malignancies and cardiovascular diseases, whose mortality exceeds the one of the disease itself, with long-term follow-up. The current therapeutic strategy in HL, based on the assessment of initial risk factors, is the result of large clinical trials led by the main international cooperating groups...
December 27, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29274233/efficacy-of-anti-pd-1-on-skin-carcinomas-and-melanoma-metastases-in-an-xeroderma-pigmentosum-patient
#13
G Salomon, A Maza, S Boulinguez, C Paul, L Lamant, E Tournier, J Mazereeuw-Hautier, N Meyer
Xeroderma pigmentosum is an orphan disease of poor prognosis. We report one case of parallel efficacy with anti-PD-1 antibody on both melanoma and skin carcinoma in a xeroderma pigmentosum patient. A 17-year old patient presented with metastatic melanoma and multiple non melanoma skin cancers. He was treated with pembrolizumab, a monoclonal anti-PD-1 antibody, at the dose of 2mg/Kg 3 weeks apart. Parallel therapeutic efficacy of anti-PD1 was observed in metastatic melanoma and skin carcinomas, and maintained at week 24...
December 23, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29247829/pd-1-modulates-radiation-induced-cardiac-toxicity-through-cytotoxic-t-lymphocytes
#14
Shisuo Du, Lin Zhou, Gregory S Alexander, Kyewon Park, Lifeng Yang, Nadan Wang, Xinliang Ma, Yajing Wang, Adam P Dicker, Bo Lu
INTRODUCTION: Combined immune checkpoint blockade has led to rare autoimmune complications, such as fatal myocarditis. Recent approvals of several anti-PD1 drugs for lung cancer treatment prompted ongoing clinical trials that directly combine PD-1 inhibitors with thoracic radiotherapy for locally advanced lung cancer. Overlapping toxicities from either modality have the potential to increase the risk for radiation-induced cardiotoxicity (RICT), which is well documented among patients with HD and breast cancer...
December 13, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29241546/neutrophils-and-snail-orchestrate-the-establishment-of-a-pro-tumor-microenvironment-in-lung-cancer
#15
Julien Faget, Svenja Groeneveld, Gael Boivin, Martial Sankar, Nadine Zangger, Miguel Garcia, Nicolas Guex, Inti Zlobec, Loïc Steiner, Alessandra Piersigilli, Ioannis Xenarios, Etienne Meylan
Understanding the immune compartment of tumors facilitates the development of revolutionary new therapies. We used a Kras(G12D)-driven mouse model of lung cancer to establish an immune signature and identified a contribution of Gr1+ neutrophils to disease progression. Depletion experiments showed that Gr1+ cells (1) favor tumor growth, (2) reduce T cell homing and prevent successful anti-PD1 immunotherapy, and (3) alter angiogenesis, leading to hypoxia and sustained Snail expression in lung cancer cells. In turn, Snail accelerated disease progression and increased intratumoral Cxcl2 secretion and neutrophil infiltration...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29239193/-checkpoint-inhibitors-in-the-treatment-of-upper-gastrointestinal-tract-tumors
#16
R Obermannova
Chemotherapy prolongs overall survival (OS) in esophageal (EC) and gastric cancer (GC). Unsatisfactory results of systemic therapy initiated a search for new treatment options. In metastatic disease, a number of targeted drugs were tested; however, several phase III studies assessing receptor tyrosin kinase-related signaling pathways, such as EGFR, MET/HGF or mTOR, failed. Trastuzumab remains the only targeted drug with a known molecular predictor, which extended the OS in metastatic gastric adenocarcinoma and adenocarcinoma of esophago-gastric junction...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29228696/mp0250-a-vegf-and-hgf-neutralizing-darpin%C3%A2-molecule-shows-high-anti-tumor-efficacy-in-mouse-xenograft-and-patient-derived-tumor-models
#17
Ulrike Fiedler, Savira Ekawardhani, Andreas Cornelius, Pat Gilboy, Talitha R Bakker, Ignacio Dolado, Michael T Stumpp, Keith M Dawson
Background: The VEGF/VEGFR and the HGF/cMET pathways are key mediators of the interplay of tumor cells and their microenvironment. However, inhibition of VEGF has been shown to produce only limited clinical benefit and inhibition of the activation of cMET by HGF has not translated into clinical benefit in pivotal trials. MP0250, a DARPin® molecule that specifically inhibits both VEGF and HGF has been developed to explore the clinical potential of dual inhibition of these pathways. Results: MP0250 binding to VEGF and HGF inhibited downstream signalling through VEGFR2 and cMET resulting in inhibition of proliferation of VEGF- and HGF-dependent cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228559/initial-experience-of-anti-pd1-therapy-with-nivolumab-in-advanced-hepatocellular-carcinoma
#18
Duan Feng, Xie Hui, Lu Shi-Chun, Bai Yan-Hua, Cui Li, Li Xiao-Hui, Yan Jie-Yu
Purpose: To evaluate efficacy and safety of anti-PD1 therapy with nivolumab for treatment of advanced hepatocellular carcinoma (HCC). Methods: From Jan 2016 to Jan 2017, eleven cases of HCC (average age of 51.8-year), 4 at stage B and 7 at stage C, according to Barcelona Clinic Liver Cancer staging, were treated with nivolumab. There were 4 patients with lung metastasis, 1 with portal vein tumor thrombus, 1 with abdominal metastasis and 1 with bone metastasis. The protocol was nivolumab, 3 mg/kg, on day 1, q3w...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227333/illustrative-cases-for-monitoring-by-quantitative-analysis-of-braf-nras-ctdna-mutations-in-liquid-biopsies-of-metastatic-melanoma-patients-who-gained-clinical-benefits-from-anti-pd1-antibody-therapy
#19
Teofila Seremet, Simon Planken, Max Schreuer, Yanina Jansen, Mélanie Delaunoy, Hakim El Housni, Danielle Lienard, Véronique Del Marmol, Pierre Heimann, Bart Neyns
Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of metastatic melanoma patients. Predictive or monitoring biomarkers for response to this therapy could improve the clinical management of these patients. To date, no established biomarkers are available for monitoring the response to immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as BRAF and NRAS mutations for melanoma patients have been proposed for monitoring of immunotherapy response. We present seven illustrative cases for the use of ctDNA BRAF and NRAS mutations' monitoring in plasma...
December 8, 2017: Melanoma Research
https://www.readbyqxmd.com/read/29226090/inhibition-of-il-18-mediated-myeloid-derived-suppressor-cell-accumulation-enhances-anti-pd1-efficacy-against-osteosarcoma-cancer
#20
Ying Guan, Rui Zhang, Zhibin Peng, Daming Dong, Guojun Wei, Yansong Wang
Myeloid derived suppressor cells (MDSC) are very important in tumor immune evasion and they dramatically increased in peripheral blood of patients with osteosarcoma cancer. The association between MDSC and various cytokines has been studied in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and interleukin 18 (IL-18) level in osteosarcoma tumor model and its effect on the immunotherapy. MDSC were isolated from the blood and parenchyma and analyzed in the osteosarcoma tumor model...
November 2017: Journal of Bone Oncology
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