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https://www.readbyqxmd.com/read/28429196/expression-of-programmed-cell-death-protein-1-by-tumor-infiltrating-lymphocytes-and-tumor-cells-is-associated-with-advanced-tumor-stage-in-patients-with-esophageal-adenocarcinoma
#1
Dagmar Kollmann, Desislava Ignatova, Julia Jedamzik, Yun-Tsan Chang, Gerd Jomrich, Matthias Paireder, Ivan Kristo, Dmitry Kazakov, Michal Michal, Antonio Cozzio, Wolfram Hoetzenecker, Tobias Schatton, Reza Asari, Matthias Preusser, Emmanuella Guenova, Sebastian F Schoppmann
BACKGROUND: Despite recent advances in the therapy for adenocarcinoma of the esophagogastric junction (AEG), overall prognosis remains poor. Programmed cell death protein 1 (PD1) is a co-inhibitory receptor primarily expressed by T-cells. Tumor cells can escape anticancer immune responses by triggering the PD1 pathway. Moreover, PD1 receptor engagement on cancer cells may trigger tumor-intrinsic growth signals. This study aimed to evaluate the potential clinical relevance of PD1 expression by tumor-infiltrating lymphocytes (TILs) and cancer cells in the AEG...
April 20, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28428203/tslp-activated-dendritic-cells-induce-human-t-follicular-helper-cell-differentiation-through-ox40-ligand
#2
Lucia Pattarini, Coline Trichot, Sofia Bogiatzi, Maximilien Grandclaudon, Stephan Meller, Zela Keuylian, Melanie Durand, Elisabetta Volpe, Stefania Madonna, Andrea Cavani, Andrea Chiricozzi, Marco Romanelli, Toshiyuki Hori, Alain Hovnanian, Bernhard Homey, Vassili Soumelis
T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells...
April 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28426103/neurotoxicity-from-immune-checkpoint-inhibition-in-the-treatment-of-melanoma-a-single-centre-experience-and-review-of-the-literature
#3
L Spain, G Walls, M Julve, K O'Meara, T Schmid, E Kalaitzaki, S Turajlic, M Gore, J Rees, J Larkin
Background: Treatment with immune checkpoint inhibitors (ICPi) has greatly improved survival for patients with advanced melanoma in recent years. Anti-CTLA-4 and anti-PD1 antibodies have been approved following large Phase III trials. Immune-related neurological toxicity of varying severity has been reported in the literature. The cumulative incidence of neurotoxicity among ipilimumab, nivolumab and pembrolizumab is reported as <1% in published clinical trials. We aimed to identify the incidence of neurotoxicity in our institution across anti-CTLA4 and anti-PD-1 antibodies, including the combination of ipilimumab with nivolumab...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28420659/very-low-expression-of-pd-l1-in-medullary-thyroid-carcinoma
#4
Massimo Bongiovanni, Caterina Rebecchini, Chiara Saglietti, Jean-Luc Bulliard, Laura Marino, Laurence De Leval, Gerasimos P Sykiotis
Monoclonal antibodies that inhibit the interaction between PD1 and PD-L1 are approved for clinical use in several cancer types, and they are also in clinical trials for additional indications, including thyroid carcinomas. A few papers have reported on PD-L1 expression in thyroid carcinomas, including a recent large study by Ahn et al. in Endocrine-Related Cancer using tissue microarrays on differentiated and anaplastic thyroid carcinoma. However, the expression of PD-L1 in medullary thyroid carcinoma (MTC) has not been reported so far, even though ongoing clinical studies aim to test the effectiveness of checkpoint inhibitors in this rare histotype as well...
April 18, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28415570/meta-analysis-of-programmed-cell-death-1-polymorphisms-with-systemic-lupus-erythematosus-risk
#5
REVIEW
Jie Gao, Nan Gai, Li Wang, Kang Liu, Xing-Han Liu, Lin-Ting Wei, Tian Tian, Shan-Li Li, Yi Zheng, Yu-Jiao Deng, Zhi-Jun Dai, Rong-Guo Fu
The association of polymorphisms in programmed cell death 1 (PDCD1) gene with systemic lupus erythematosus (SLE) risk is inconsistent across different studies. This meta-analysis is aimed to provide reliable evidence to the association of five common PDCD1 polymorphisms (PD1.1, PD1.2, PD1.3, PD1.5 and PD1.6) with SLE risk. A total of 28 studies with 4,344 SLE cases and 5,474 healthy controls were included in this meta-analysis. PD1.3 polymorphism was significantly associated with SLE in the overall population (A vs...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414668/autoimmune-diabetes-presented-with-diabetic-ketoacidosis-induced-by-immunotherapy-in-an-adult-with-melanoma
#6
A A Alzenaidi, J Dendy, L Rejjal
INTRODUCTION: Immunotherapy has been approved for treatment of melanoma. Autoimmune endocrinopathies have been reported in trials involving immunotherapy but autoimmune diabetes has not been definitively linked to them. Here we describe a case of autoimmune diabetes presenting with DKA after receiving combined immunotherapy with anti-CTLA4 and anti-PD1 monoclonal antibodies. CASE: A 47year old gentleman with metastatic melanoma presented to our institution with confusion, abdominal pain and decreased oral intake...
March 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28414090/rituximab-treatment-circumvents-the-prognostic-impact-of-tumor-infiltrating-t-cells-in-follicular-lymphoma-patients
#7
Luc Xerri, Sarah Huet, Jeffrey M Venstrom, Edith Szafer-Glusman, Bettina Fabiani, Danielle Canioni, Catherine Chassagne-Clément, Peggy Dartigues-Cuilléres, Fréderic Charlotte, Camille Laurent, Benedicte Gelas-Dore, Christopher R Bolen, Elizabeth Punnoose, Reda Bouabdallah, Pauline Brice, Franck Morschhauser, Guillaume Cartron, Daniel Olive, Gilles Salles
Previous immunohistochemical (IHC) studies showed controversial data about the prognostic value of tumor infiltrating lymphocytes (TIL) in follicular lymphoma (FL). In order to clarify this issue, a large series of FL samples from rituximab-treated patients enrolled in the randomized PRIMA trial were examined. IHC was quantified using automated image analysis in 417, 287, 418, 406, 379, and 369 patients for CD3, CD4, CD8, PD1, ICOS, and FOXP3; respectively. RNAseq analysis was used to quantify TIL-related mRNA transcripts from 148 patients...
April 13, 2017: Human Pathology
https://www.readbyqxmd.com/read/28407528/immunotherapy-revolutionises-non-small-cell-lung-cancer-therapy-results-perspectives-and-new-challenges
#8
REVIEW
Etienne Giroux Leprieur, Coraline Dumenil, Catherine Julie, Violaine Giraud, Jennifer Dumoulin, Sylvie Labrune, Thierry Chinet
Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10...
April 10, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28407370/inflammation-triggered-cancer-immunotherapy-by-programmed-delivery-of-cpg-and-anti-pd1-antibody
#9
Chao Wang, Wujin Sun, Grace Wright, Andrew Z Wang, Zhen Gu
No abstract text is available yet for this article.
April 2017: Advanced Materials
https://www.readbyqxmd.com/read/28405501/pdl1-expression-is-a-poor-prognosis-factor-in-soft-tissue-sarcomas
#10
François Bertucci, Pascal Finetti, Delphine Perrot, Agnès Leroux, Françoise Collin, Axel Le Cesne, Jean-Michel Coindre, Jean-Yves Blay, Daniel Birnbaum, Emilie Mamessier
Soft-tissue sarcomas (STS) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. In the quest for new treatments, the immune system represents an attractive therapeutic target. Recently, PD1/PDL1 inhibitors showed very promising results in patients with solid tumors. PDL1 expression has been rarely studied in STS, in small series only, by using immunohistochemistry (IHC), and with non-concordant prognostic implications. Here, we have analyzed PDL1 mRNA expression in 758 clinical STS samples retrospectively profiled using DNA microarrays and RNAseq, and searched for correlations with clinicopathological variables including metastasis-free survival (MFS) after surgery...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28404956/cabazitaxel-in-recurrent-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-phase-ii-unicancer-trial-orl03
#11
Jerome Fayette, Joel Guigay, Christophe Le Tourneau, Marian Degardin, Frederic Peyrade, Eve-Marie Neidhardt, Marie-Paule Sablin, Caroline Even, Florence Orlandini, Béata Juzyna, Carine Bellera
Treatments are limited after platinum Cetuximab or anti-PD1 failure for patients with recurrent/metastatic head and neck squamous cell carcinoma. Cabazitaxel has increased overall survival in hormone-refractory metastatic prostate cancer after failure of Docetaxel. Our aim was to detect a signal of activity with Cabazitaxel in patients with head and neck cancer who had failed platinum-, Cetuximab- and taxanes-based chemotherapy.This multicenter phase II trial included progressive patients with an ECOG ≤2...
March 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400429/genomic-analysis-of-thymic-epithelial-tumors-identifies-novel-subtypes-associated-with-distinct-clinical-features
#12
Hyun-Sung Lee, Hee-Jin Jang, Rohan Shah, David Yoon, Masatsugu Hamaji, Ori Wald, Ju-Seog Lee, David J Sugarbaker, Bryan M Burt
PURPOSE To reconcile the heterogeneity of thymic epithelial tumors (TETs) and gain deeper understanding of the molecular determinants of TETs, we set out to establish a clinically relevant molecular classification system for these tumors. <p>EXPERIMENTAL DESIGN Molecular subgrouping of TETs was performed in 120 patients from The Cancer Genome Atlas using a multidimensional approach incorporating analyses of DNA mutations, mRNA expression, and somatic copy number alterations (SCNA), and validated in two independent cohorts...
April 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28396974/sarcopenic-overweight-is-associated-with-early-acute-limiting-toxicity-of-anti-pd1-checkpoint-inhibitors-in-melanoma-patients
#13
Heidelberger Valentine, Goldwasser François, Kramkimel Nora, Jouinot Anne, Huillard Olivier, Boudou-Rouquette Pascaline, Chanal Johan, Arrondeau Jennifer, Franck Nathalie, Alexandre Jérôme, Blanchet Benoît, Leroy Karen, Avril Marie-Françoise, Dupin Nicolas, Aractingi Sélim
Little is known on factors predicting toxicity of anti-PD1 checkpoint inhibitors. Sarcopenic obesity is associated with increased acute toxicity of cytotoxic agents and targeted therapies. We explored whether body composition also influenced the occurrence of early acute limiting toxicity (ALT) of anti-PD1 in melanoma patients. This is a monocentric, retrospective study analyzing toxicity outcome in consecutive melanoma patients treated with nivolumab or pembrolizumab. Various parameters linked to the patient or the disease status have been analysed...
April 10, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28389693/the-advantages-and-challenges-of-using-fdg-pet-ct-for-response-assessment-in-melanoma-in-the-era-of-targeted-agents-and-immunotherapy
#14
REVIEW
Annie N M Wong, Grant A McArthur, Michael S Hofman, Rodney J Hicks
The treatment of melanoma has been revolutionised in recent years by advances in the understanding of the genomic landscape of this disease, which has led to the development of new targeted therapeutic agents, and the ability to therapeutically manipulate the immune system through inhibition of cancer cell-T-cell interactions that prevent an adaptive immune response. While these therapeutic interventions have dramatically improved the prospects of survival for patients with advanced melanoma, they bring significant complexity to the interpretation of therapeutic response because their mechanisms and temporal profile of response vary considerably...
April 7, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28383817/cd70-and-pdl1-in-anaplastic-thyroid-cancer-ndash-promising-targets-for-immunotherapy
#15
Karen Zwaenepoel, Julie Jacobs, Astrid De Meulenaere, Karen Silence, Evelien Smits, Vasiliki Siozopoulou, Esther Hauben, Christian Rolfo, Sylvie Rottey, Patrick Pauwels
AIMS: Over the last years, immune checkpoint inhibition has proven to be effective in several solid malignancies. The aim of this study was to identify novel targets for immunotherapy in anaplastic thyroid cancer by analysis of the expression of tumor antigens for which therapeutic agents are available. METHOD AND RESULTS: By immunohistochemistry we observed tumoral expression of CD70 in 49% of cases. Expression of its receptor, CD27 was mainly present in lymphocytes surrounding and infiltrating the tumor and only rarely observed in tumor cells...
April 6, 2017: Histopathology
https://www.readbyqxmd.com/read/28367063/understanding-the-role-of-pd-l1-pd1-pathway-blockade-and-autophagy-in-cancer-therapy
#16
REVIEW
Marianela Robainas, Rafael Otano, Stephen Bueno, Sihem Ait-Oudhia
Autophagy is a vital, physiological catabolic process for cell survival by which cells clear damaged organelles and recycle nutrients when homeostasis is maintained. Cancer is a complex disease with uncontrolled growth of cancer cells. Recent studies have suggested the role of autophagy in cancer. A complex relationship exists between autophagy and cancer, since autophagy can contribute to the survival or the destruction of malignant cells depending on the stage of tumor development. In this review, we describe in detail the mechanism underlying autophagy in cancer cells and the intricate involvement of the programmed cell death-1 (PD1) receptor with its ligand (PD-L1)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28356247/pd-1-blockade-with-nivolumab-in-relapsed-refractory-primary-central-nervous-system-and-testicular-lymphoma
#17
Lakshmi Nayak, Fabio M Iwamoto, Ann LaCasce, Srinivasan Mukundan, Margaretha G M Roemer, Bjoern Chapuy, Philippe Armand, Scott J Rodig, Margaret A Shipp
Primary central nervous system lymphoma (PCNSL) and primary testicular lymphoma (PTL) are rare extranodal large B-cell lymphomas with similar genetic signatures. There are no standard of care treatment options for patients with relapsed and refractory PCNSL and PTL, and the overall prognosis is poor. PCNSLs and PTLs exhibit frequent 9p24.1 copy number alterations and infrequent translocations of 9p24.1 and associated increased expression of the programmed cell death protein 1 (PD-1) ligands PD-L1 and PD-L2...
March 29, 2017: Blood
https://www.readbyqxmd.com/read/28351930/hyper-progressors-after-immunotherapy-analysis-of-genomic-alterations-associated-with-accelerated-growth-rate
#18
Shumei Kato, Aaron Michael Goodman, Vighnesh Walavalkar, Donald A Barkauskas, Andrew Sharabi, Razelle Kurzrock
PURPOSE: Checkpoint inhibitors demonstrate salutary anti-cancer effects including long-term remissions. PD-L1 expression/amplification, high mutational burden and mismatch repair-deficiency correlate with response. We have, however, observed a subset of patients who appear to be "hyper-progressors," with a greatly accelerated rate of tumor growth and clinical deterioration compared to pre-therapy, which was also recently reported by Institut Gustave Roussy. The current study investigated potential genomic markers associated with "hyper-progression" after immunotherapy...
March 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28349740/immunotherapy-for-gastric-cancers-emerging-role-and-future-perspectives
#19
Marta Bonotto, Silvio Ken Garattini, Debora Basile, Elena Ongaro, Valentina Fanotto, Monica Cattaneo, Francesco Cortiula, Donatella Iacono, Giovanni Gerardo Cardellino, Nicoletta Pella, Gianpiero Fasola, Lorenzo Antonuzzo, Nicola Silvestris, Giuseppe Aprile
The broad use of immunotherapy is revolutionizing the treatment paradigms of many solid tumors. Although chemotherapy remains the treatment backbone for advanced gastric cancer, improvements in its molecular characterization and progresses in understanding its underpinning biology have supported clinical development of novel immunotherapies. However, the results of recent trials testing these new agents raise the question on how to identify the patients that could greatly benefit. Areas covered: This article summarizes the current understanding on the biology and the mechanisms underlying different clinical features of gastric cancers...
March 28, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28348944/tumoral-melanosis-associated-with-pembrolizumab-treated-metastatic-melanoma
#20
Omar Bari, Philip R Cohen
Tumoral melanosis is a form of completely regressed melanoma that usually presents as darkly pigmented lesions suspicious for malignant melanoma. Histology reveals dense dermal and subcutaneous infiltration of melanophages. Pembrolizumab is an antibody directed against programmed death receptor-1 (PD1) and is frontline treatment for advanced melanoma. An 81-year-old man with metastatic melanoma treated with pembrolizumab who developed tumoral melanosis at previous sites of metastases is described. The PubMed database was searched with the key words: antibody, immunotherapy, melanoma, melanosis, metastasis, pembrolizumab, and tumoral...
February 13, 2017: Curēus
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