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Anti pd1

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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
#1
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
#2
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
#3
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
#4
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/29327244/antibody-based-delivery-of-tumor-necrosis-factor-l19-tnf%C3%AE-and-interleukin-2-l19-il2-to-tumor-associated-blood-vessels-has-potent-immunological-and-anticancer-activity-in-the-syngeneic-j558l-balb-c-myeloma-model
#5
Hans D Menssen, Ulf Harnack, Ulrike Erben, Dario Neri, Burkhard Hirsch, Horst Dürkop
PURPOSE: To analyze the impact of TNFα or IL2 on human lymphocytes in vitro and the anti-tumor and immune-modifying effects of L19-IL2 and L19-TNFα on subcutaneously growing J558L myeloma in immunocompetent mice. METHODS: PBMCs from three healthy volunteers were incubated with IL2, TNFα, or with IL2 plus addition of TNFα (final 20 h). BALB/c J558L mice with subcutaneous tumors were treated with intravenous L19-TNFα plus L19-IL2, or controls. Tumor growth and intra- and peri-tumoral tissues were analyzed for micro-vessel density, necrosis, immune cell composition, and PD1 or PD-L1 expressing cells...
January 11, 2018: Journal of Cancer Research and Clinical Oncology
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/29309291/bullous-pemphigoid-like-skin-lesions-and-overt-eosinophilia-in-a-patient-with-melanoma-treated-with-nivolumab-case-report-and-review-of-the-literature
#10
Amalia Anastasopoulou, Georgios Papaxoinis, Panagiotis Diamantopoulos, Erietta Christofidou, Olga Benopoulou, Alexandros Stratigos, Helen Gogas
The widespread use of immune checkpoint inhibitors has shed light to several unusual immune-related adverse effects of the drugs. Severe cutaneous adverse reactions are generally rare with anti-PD1 agents. We present in this paper the case of a 48-year-old patient with melanoma who developed bullous pemphigoid-like skin lesions along with fever, arthralgia and overt eosinophilia following adjuvant treatment with nivolumab. The condition was successfully treated with corticosteroids and a rechallenge with another anti-PD1 agent did not lead to recurrence of the skin lesions...
January 5, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29309048/early-b-cell-changes-predict-autoimmunity-following-combination-immune-checkpoint-blockade
#11
Rituparna Das, Noffar Bar, Michelle Ferreira, Aaron M Newman, Lin Zhang, Jithendra Kini Bailur, Antonella Bacchiocchi, Harriet Kluger, Wei Wei, Ruth Halaban, Mario Sznol, Madhav V Dhodapkar, Kavita M Dhodapkar
Combination checkpoint blockade (CCB) targeting inhibitory CTLA4 and PD1 receptors holds promise for cancer therapy. Immune-related adverse events (IRAEs) remain a major obstacle for the optimal application of CCB in cancer. Here, we analyzed B cell changes in patients with melanoma following treatment with either anti-CTLA4 or anti-PD1, or in combination. CCB therapy led to changes in circulating B cells that were detectable after the first cycle of therapy and characterized by a decline in circulating B cells and an increase in CD21lo B cells and plasmablasts...
January 8, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29308326/depletion-of-tumor-associated-macrophages-switches-the-epigenetic-profile-of-pancreatic-cancer-infiltrating-t-cells-and-restores-their-anti-tumor-phenotype
#12
Simone Borgoni, Andrea Iannello, Santina Cutrupi, Paola Allavena, Maurizio D'Incalci, Francesco Novelli, Paola Cappello
Pancreatic Ductal Adenocarcinoma (PDA) is characterized by a complex tumor microenvironment that supports its progression, aggressiveness and resistance to therapies. The delicate interplay between cancer and immune cells creates the conditions for PDA development, particularly due to the functional suppression of T cell anti-tumor effector activity. However, some of the mechanisms involved in this process are still poorly understood. In this study, we analyze whether the functional and epigenetic profile of T cells that infiltrate PDA is modulated by the microenvironment, and in particular by tumor-associated macrophages (TAMs)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308318/the-inhibitory-checkpoint-pd-l2-is-a-target-for-effector-t-cells-novel-possibilities-for-immune-therapy
#13
Shamaila Munir Ahmad, Evelina Martinenaite, Morten Holmström, Mia Aaboe Jørgensen, Özcan Met, Claudia Nastasi, Uffe Klausen, Marco Donia, Lars Møller Pedersen, Lars Munksgaard, Niels Ødum, Anders Woetmann, Inge Marie Svane, Mads Hald Andersen
Cell surface molecules of the B7/CD28 family play an important role in T-cell activation and tolerance. The relevance of the PD-1/PD-L1 pathway in cancer has been extensively studied whereas PD-L2 has received less attention. However, recently the expression of PD-L2 was described to be independently associated with clinical response in anti-PD1-treated cancer patients. Here, we investigated whether PD-L2 might represent a natural target that induces specific T cells. We identified spontaneous specific T-cell reactivity against two epitopes located in the signal peptide of PD-L2 from samples from patients with cancer as well as healthy individuals ex vivo...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29303012/blockade-of-ccr5-mediated-myeloid-derived-suppressor-cell-accumulation-enhances-anti-pd1-efficacy-in-gastric-cancer
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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