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https://www.readbyqxmd.com/read/29444608/acute-autoimmune-myocarditis-and-hepatitis-due-to-ipilimumab-monotherapy-for-malignant-melanoma
#1
Yazeed Samara, Chun Lai Yu, Constantin A Dasanu
An important agent in melanoma therapy, ipilimumab is associated with autoimmune toxicity. Two cases of autoimmune pericarditis and large pericardial effusion have been documented with its use. Reports of myocardial toxicity have surfaced with this agent, mainly when used in combination with PD1 blockade. We present herein a case of autoimmune myocarditis leading to biventricular failure after four doses of IV ipilimumab 3 mg/kg as a single agent. Furthermore, this toxic effect may be anticipated with PD1 inhibitors...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29439955/dual-pd1-lag3-immune-checkpoint-blockade-limits-tumor-development-in-a-murine-model-of-chronic-lymphocytic-leukemia
#2
Marina Wierz, Sandrine Pierson, Léa Guyonnet, Elodie Viry, Audrey Lequeux, Anaïs Oudin, Simone P Niclou, Markus Ollert, Guy Berchem, Bassam Janji, Coralie Guérin, Jerome Paggetti, Etienne Moussay
No abstract text is available yet for this article.
February 13, 2018: Blood
https://www.readbyqxmd.com/read/29434933/pd-l1-expression-is-associated-with-p16-ink4a-expression-in-non-oropharyngeal-head-and-neck-squamous-cell-carcinoma
#3
San-Chi Chen, Peter Mu-Hsin Chang, Hsiao-Jung Wang, Shyh-Kuan Tai, Pen-Yuan Chu, Muh-Hwa Yang
PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD-L1 expression in non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non-OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin-embedded non-OPHNSCC samples obtained from patients were constructed, and PD-L1 and p16 INK4A expression were determined using immunohistochemistry...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434366/potentiating-prostate-cancer-immunotherapy-with-oncolytic-viruses
#4
REVIEW
Patrick Lee, Shashi Gujar
The clinical effectiveness of immunotherapies for prostate cancer remains subpar compared with that for other cancers. The goal of most immunotherapies is the activation of immune effectors, such as T cells and natural killer cells, as the presence of these activated mediators positively correlates with patient outcomes. Clinical evidence shows that prostate cancer is immunogenic, accessible to the immune system, and can be targeted by antitumour immune responses. However, owing to the detrimental effects of prostate-cancer-associated immunosuppression, even the newest immunotherapeutic approaches fail to initiate the clinically desired antitumour immune reaction...
February 13, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29434283/the-wavelength-of-the-incident-light-determines-the-primary-charge-separation-pathway-in-photosystem-ii
#5
Andrea Pavlou, Julien Jacques, Nigar Ahmadova, Fikret Mamedov, Stenbjörn Styring
Charge separation is a key component of the reactions cascade of photosynthesis, by which solar energy is converted to chemical energy. From this photochemical reaction, two radicals of opposite charge are formed, a highly reducing anion and a highly oxidising cation. We have previously proposed that the cation after far-red light excitation is located on a component different from PD1, which is the location of the primary electron hole after visible light excitation. Here, we attempt to provide further insight into the location of the primary charge separation upon far-red light excitation of PS II, using the EPR signal of the spin polarized 3P680 as a probe...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29433938/b-cell-lymphoma-immunotherapy-using-tlr9-targeted-oligonucleotide-stat3-inhibitors
#6
Xingli Zhao, Zhuoran Zhang, Dayson Moreira, Yu-Lin Su, Haejung Won, Tomasz Adamus, Zhenyuan Dong, Yong Liang, Hongwei H Yin, Piotr Swiderski, Raju K Pillai, Larry Kwak, Stephen Forman, Marcin Kortylewski
Growing evidence links the aggressiveness of non-Hodgkin's lymphoma, especially the activated B cell-like type diffuse large B cell lymphomas (ABC-DLBCLs) to Toll-like receptor 9 (TLR9)/MyD88 and STAT3 transcription factor signaling. Here, we describe a dual-function molecule consisting of a clinically relevant TLR9 agonist (CpG7909) and a STAT3 inhibitor in the form of a high-affinity decoy oligodeoxynucleotide (dODN). The CpG-STAT3dODN blocked STAT3 DNA binding and activity, thus reducing expression of downstream target genes, such as MYC and BCL2L1, in human and mouse lymphoma cells...
January 17, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29432222/immunotherapy-for-recurrent-metastatic-head-and-neck-cancer
#7
Salvatore Alfieri, Stefano Cavalieri, Lisa Licitra
PURPOSE OF REVIEW: In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less 'immunogenic' than other malignancies (e...
February 8, 2018: Current Opinion in Otolaryngology & Head and Neck Surgery
https://www.readbyqxmd.com/read/29427592/establishment-of-engineered-cell-based-assays-mediating-lag3-and-pd1-immune-suppression-enables-potency-measurement-of-blocking-antibodies-and-assessment-of-signal-transduction
#8
Bhagyashree Bhagwat, Holly Cherwinski, Manjiri Sathe, Wolfgang Seghezzi, Terrill K McClanahan, Rene de Waal Malefyt, Aarron Willingham
LAG3 is an important regulator of T cell homeostasis and studies in mouse tumor models have demonstrated that simultaneously antagonizing LAG3 and PD1 can augment tumor-specific T cell responses and induce tumor rejection. The combined use of LAG3 antagonist antibodies with established anti-PD1 therapies is currently being evaluated in human clinical trials. A functional assay for human LAG3 was developed by co-culture of a Jurkat T-cell lymphoma line overexpressing LAG3 with a Raji B-cell lymphoma line in the presence of staphylococcal enterotoxins...
February 7, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29423108/cancer-immunogenomic-approach-to-neoantigen-discovery-in-a-checkpoint-blockade-responsive-murine-model-of-oral-cavity-squamous-cell-carcinoma
#9
Paul Zolkind, Dariusz Przybylski, Nemanja Marjanovic, Lan Nguyen, Tianxiang Lin, Tanner Johanns, Anton Alexandrov, Liye Zhou, Clint T Allen, Alexander P Miceli, Robert D Schreiber, Maxim Artyomov, Gavin P Dunn, Ravindra Uppaluri
Head and neck squamous cell carcinomas (HNSCC) are an ideal immunotherapy target due to their high mutation burden and frequent infiltration with lymphocytes. Preclinical models to investigate targeted and combination therapies as well as defining biomarkers to guide treatment represent an important need in the field. Immunogenomics approaches have illuminated the role of mutation-derived tumor neoantigens as potential biomarkers of response to checkpoint blockade as well as representing therapeutic vaccines...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29421981/standing-in-the-gap-to-formulate-a-novel-radioimmunotherapy-regime-to-improve-the-long-term-outcome-in-breast-cancer
#10
Ho Liam Pock, Teo Yi Wei Bryan, Tan Puay Hoon, Jabed Iqbal, Linn Yeh Ching, Goh Yeow Tee, Tan Kar Wai, Toh Han Chong, Ong Kong Wee, Yeoh Kheng Wei
AIM: The new radioimmunotherapeutic regime GAP15R aims to stimulate glucocorticoid-induced TNF-related protein (G) to overcome Treg suppression; add IFN-α (A) to promote inflammatory milieu; block PD1 (P) to disinhibit T effector cytotoxicity; add IL-15 (15) to enhance danger signals & T-cell expansion; and apply radiation (R) at critical time point to sustain localized inflammation. Patients & methods/materials & methods: This was tested in a murine 4T1 metastatic breast carcinoma model given GAP15R with regular monitoring of tumor volume and complications...
February 1, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29416916/genotyping-and-mrna-profiling-reveal-actionable-molecular-targets-in-biliary-tract-cancers
#11
Kyriaki Papadopoulou, Samuel Murray, Kyriaki Manousou, Ioannis Tikas, Christos Dervenis, Joseph Sgouros, Dimitra Rontogianni, Sotirios Lakis, Mattheos Bobos, Christos Poulios, Stavroula Pervana, Georgios Lazaridis, George Fountzilas, Vassiliki Kotoula
Biliary tract cancer (BTC) represents a heterogeneous disease with dismal outcome. Herein, we examined genotype and angiogenesis features in BTC. We applied genotyping (Sanger, qPCR, 101-gene panel NGS), mRNA relative quantification methods, and β-catenin immunohistochemistry in 84 FFPE BTC (55 gallbladder [GBC], 14 intrahepatic [ICC], 15 extrahepatic [ECC] carcinomas). We identified 541 mutations in 68 (81%) tumors. Top mutated genes were CTNNB1 (36%); PTEN (33%); TP53 (31%); PIK3R1 (29%); PIK3CA (13%); BRCA2 and KRAS (12%); BRCA1 (11%)...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29410200/a-web-platform-for-the-network-analysis-of-highthroughput-data-in-melanoma-and-its-use-to-investigate-mechanisms-of-resistance-to-anti-pd1-immunotherapy
#12
Florian S Dreyer, Martina Cantone, Martin Eberhardt, Tanushree Jaitly, Lisa Walter, Jürgen Wittmann, Shailendra Gupta, Faiz Khan, Olaf Wolkenhauer, Brigitte Pützer, Hans-Martin Jäck, Lucie Heinzerling, Julio Vera
Cellular phenotypes are established and controlled by complex and precisely orchestrated molecular networks. In cancer, mutations and dysregulations of multiple molecular factors perturb the regulation of these networks and lead to malignant transformation. High-throughput technologies are a valuable source of information to establish the complex molecular relationships behind the emergence of malignancy, but full exploitation of this massive amount of data requires bioinformatics tools that rely on network-based analysis...
February 2, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29405038/systemic-treatments-for-metastatic-cutaneous-melanoma
#13
REVIEW
Sandro Pasquali, Andreas V Hadjinicolaou, Vanna Chiarion Sileni, Carlo Riccardo Rossi, Simone Mocellin
BACKGROUND: The prognosis of people with metastatic cutaneous melanoma, a skin cancer, is generally poor. Recently, new classes of drugs (e.g. immune checkpoint inhibitors and small-molecule targeted drugs) have significantly improved patient prognosis, which has drastically changed the landscape of melanoma therapeutic management. This is an update of a Cochrane Review published in 2000. OBJECTIVES: To assess the beneficial and harmful effects of systemic treatments for metastatic cutaneous melanoma...
February 6, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29399402/prognostic-relevance-of-tumor-infiltrating-lymphocytes-and-immune-checkpoints-in-pediatric-medulloblastoma
#14
Jeroen F Vermeulen, Wim Van Hecke, Elisabeth J M Adriaansen, Mieke K Jansen, Rianne G Bouma, José Villacorta Hidalgo, Paul Fisch, Roel Broekhuizen, Wim G M Spliet, Marcel Kool, Niels Bovenschen
Pediatric medulloblastomas are the most frequently diagnosed embryonal tumors of the central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival and to avoid morbidity. Efficient killing of tumor cells using immunotherapy requires to overcome cancer-associated strategies to evade cytotoxic immune responses. Here, we examined the immune response and immune evasion strategies in pediatric medulloblastomas...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399387/analysis-of-pd1-pdl1-pdl2-expression-and-t-cells-infiltration-in-1014-gastric-cancer-patients
#15
Xiaofang Xing, Jianping Guo, Xianzi Wen, Guangyu Ding, Bo Li, Bin Dong, Qin Feng, Shen Li, Jian Zhang, Xiaojing Cheng, Ting Guo, Hong Du, Ying Hu, Xiaohong Wang, Lin Li, Qingda Li, Meng Xie, Liting Li, Xiangyu Gao, Fei Shan, Ziyu Li, Xiaomin Ying, Tao Zhou, Jiping Wang, Jiafu Ji
Although immune checkpoint blockade have demonstrated promising results, their effects on gastric cancer (GC) are under investigation. Understanding the clinical significance of PD1 and its ligands' expression, together with T cell infiltration might provide clues for biomarkers screening in GC immunotherapy. Immunohistochemistry were performed on a tissue microarray including 1,014 GC specimens using PD1, PDL1 and PDL2 antibodies. T cell markers CD3 and CD8 were also stained and quantified by automated image analysis...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29398707/the-tumour-glyco-code-as-a-novel-immune-checkpoint-for-immunotherapy
#16
REVIEW
Ernesto RodrÍguez, Sjoerd T T Schetters, Yvette van Kooyk
Tumour growth is accompanied by tumour evasion of the immune system, a process that is facilitated by immune checkpoint molecules such as programmed cell death protein 1 (PD1). However, the role of tumour glycosylation in immune evasion has mostly been overlooked, despite the fact that aberrant tumour glycosylation alters how the immune system perceives the tumour and can also induce immunosuppressive signalling through glycan-binding receptors. As such, specific glycan signatures found on tumour cells can be considered as a novel type of immune checkpoint...
February 5, 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/29395567/-immune-checkpoint-inhibitors-antibodies-to-pd1-and-pd-l1-a-new-therapeutic-weapon-against-non-small-cell-bronchial-carcinoma
#17
REVIEW
T Berghmans, B Grigoriu, J P Sculier, A P Meert
INTRODUCTION: Classical therapeutic strategy for advanced and metastatic non-small cell lung cancer, without activable oncogenic driver mutation, has been based mainly on cytotoxic chemotherapy with modest benefits in terms of increased survival. BACKGROUND: A better understanding of the mechanisms involved in the regulation of the immune system led to the development of antibodies directed against immune checkpoints such as PD-L1. The first encouraging clinical data from phase I studies assessing anti-PD1 and anti-PD-L1 antibodies have been confirmed in randomised phase III trials...
January 27, 2018: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/29391205/primary-and-metastatic-brain-cancer-genomics-and-emerging-biomarkers-for-immunomodulatory-cancer-treatment
#18
REVIEW
F Passiglia, C Caglevic, E Giovannetti, J A Pinto, P Manca, S Taverna, A Listì, I Gil-Bazo, L E Raez, A Russo, C Rolfo
Recent studies with immunomodulatory agents targeting both cytotoxic T-lymphocyte protein 4 (CTLA4) and programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) have shown to be very effective in several cancers revealing an unexpected great activity in patients with both primary and metastatic brain tumors. Combining anti-CTLA4 and anti-PD1 agents as upfront systemic therapy has revealed to further increase the clinical benefit observed with single agent, even at cost of higher toxicity. Since the brain is an immunological specialized area it's crucial to establish the specific composition of the brain tumors' microenvironment in order to predict the potential activity of immunomodulatory agents...
January 31, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29388007/the-role-of-tumor-infiltrating-lymphocytes-tils-as-a-predictive-biomarker-of-response-to-anti-pd1-therapy-in-patients-with-metastatic-non-small-cell-lung-cancer-or-metastatic-melanoma
#19
Anton Uryvaev, Maria Passhak, Dov Hershkovits, Edmond Sabo, Gil Bar-Sela
Immunotherapy plays an important role in cancer treatment. Biomarkers that can predict response, including tumor-infiltrating lymphocytes (TILs), are in the spotlight of many studies. This cohort study was designed to evaluate the role of CD4+ and CD8+ TILs as predictive factors for response to anti PD-1 treatment in patients with metastatic non-small cell lung cancer (NSCLC) or metastatic melanoma. We evaluated the expression of CD4+ and CD8+ TILs in tissue samples of 56 patients with metastatic NSCLC or melanoma treated with anti-PD1 immunotherapy...
January 31, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29386072/activity-of-pembrolizumab-in-relapsed-refractory-nk-t-cell-lymphoma
#20
Xin Li, Yasong Cheng, Mingzhi Zhang, Jiaqin Yan, Ling Li, Xiaorui Fu, Xudong Zhang, Yu Chang, Zhenchang Sun, Hui Yu, Lei Zhang, Xinhua Wang, Jingjing Wu, Zhaoming Li, Feifei Nan, Li Tian, Wencai Li, Ken H Young
Natural killer/T-cell lymphoma (NKTCL) is a rare subtype of non-Hodgkin lymphoma that is associated with a poor outcome. Currently, the treatment needs of NKTCL remain unmet, and efforts to further improve treatment are urgently needed. Herein, seven patients with NKTCL who failed to respond to various types of chemotherapies were treated with the anti-programmed death 1 (anti-PD-1) antibody pembrolizumab at 100 mg every 3 weeks. After a median of four cycles of treatment (range 2-18), four out of seven patients responded (two complete response, two partial response, overall response rate 57%)...
January 31, 2018: Journal of Hematology & Oncology
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