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https://www.readbyqxmd.com/read/28230773/programmed-death-ligand-1-pd-l1-tumor-expression-is-associated-with-a-better-prognosis-and-diabetic-disease-in-triple-negative-breast-cancer-patients
#1
Gerardo Botti, Francesca Collina, Giosuè Scognamiglio, Federica Rao, Valentina Peluso, Rossella De Cecio, Michela Piezzo, Gabriella Landi, Michelino De Laurentiis, Monica Cantile, Maurizio Di Bonito
Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28194153/nasal-polyp-derived-mesenchymal-stromal-cells-exhibit-lack-of-immune-associated-molecules-and-high-levels-of-stem-progenitor-cells-markers
#2
Pedro Wey Barbosa de Oliveira, Rogério Pezato, Juan Sebastian Henao Agudelo, Claudina Angela Perez-Novo, Wim Vanden Berghe, Niels Olsen Câmara, Danilo Candido de Almeida, Luís Carlos Gregorio
Mesenchymal stromal cells (MSCs) are considered adult progenitor stem cells and have been studied in a multitude of tissues. In this context, the microenvironment of nasal polyp tissue has several inflammatory cells, but their stroma compartment remains little elucidated. Hence, we isolated MSCs from nasal polyps Polyp-MSCs (PO-MSCs) and compared their molecular features and gene expression pattern with bone marrow-derived MSCs (BM-MSCs). Initially, both PO-MSCs and BM-MSCs were isolated, cultivated, and submitted to morphologic, differentiation, phenotypic, immunosuppressive, and gene expression assays...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28186730/engineered-hydrogen-bonded-glycopolymer-capsules-and-their-interactions-with-antigen-presenting-cells
#3
Kristian Kempe, Sue D Xiang, Paul Wilson, Md Arifur Rahim, Yi Ju, Michael R Whittaker, David M Haddleton, Magdalena Plebanski, Frank Caruso, Thomas P Davis
Hollow glycopolymer microcapsules were fabricated by hydrogen-bonded layer-by-layer (LbL) assembly, and their interactions with a set of antigen presenting cells (APCs), including dendritic cells (DCs), macrophages (MACs), and myeloid derived suppressor cells (MDSCs), were investigated. The glycopolymers were obtained by cascade postpolymerization modifications of poly(oligo(2-ethyl-2-oxazoline methacrylate)-stat-glycidyl methacrylate) involving the modification of the glycidyl groups with propargylamine and the subsequent attachment of mannose azide by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC)...
February 10, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28185198/validation-of-anti-mouse-pdl-1-goat-polyclonal-antibody-staining-with-mouse-pdl-1-in-situ-hybridization-on-adjacent-sections-of-cell-pellets-and-mouse-tumors
#4
Jacob Ricca, Mesruh Turkekul, Afsar Barlas, Dmitry Yarilin, Sho Fujisawa, Ning Fan, Matthew Brendel, Dmitriy Zamarin, Jedd D Wolchok, Katia Manova-Todorova
Finding a valid antibody to detect mouse programmed death ligand 1 (PDL-1) by immunohistochemistry or immunofluorescence staining has been notoriously difficult. Successful validation of an antibody requires the use of multiple detection methods with the ability to compare appropriate positive and negative controls. Here, we describe in detail the protocols used to validate a mouse-specific PDL-1 antibody used in immunohistochemistry staining with an mRNA in situ hybridization on adjacent sections of mouse B16 tumor...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27911476/nd-yag-and-pulsed-dye-laser-therapy-in-infantile-haemangiomas-a-retrospective-analysis-of-271-treated-haemangiomas-in-149-children
#5
F Hartmann, A Lockmann, L-L Grönemeyer, H A Haenssle, M Zutt, H von Fintel, I Kühnle, M P Schön, K-M Thoms
BACKGROUND: Infantile haemangiomas (IH) are common benign tumours in infancy. Most IH resolve spontaneously, but some require treatment due to ulceration, functional impairment or cosmetic disfiguration. While systemic propranolol is effective in many cases, laser therapy may be a safe topical alternative. OBJECTIVE: To assess the efficacy of combined Nd:YAG/pulsed dye laser (PDL) or PDL alone for therapy of IH. PATIENTS AND METHODS: A total of 271 IH in 149 infants were treated with combined Nd:YAG/PDL or PDL alone...
December 2, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/27816392/assessing-pdl-1-and-pd-1-in-non-small-cell-lung-cancer-a-novel-immunoscore-approach
#6
Erna-Elise Paulsen, Thomas K Kilvaer, Mehrdad Rakaee Khanehkenari, Samer Al-Saad, Sigurd M Hald, Sigve Andersen, Elin Richardsen, Nora Ness, Lill-Tove Busund, Roy M Bremnes, Tom Donnem
INTRODUCTION: Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand, PD-L1, have gained momentum in the treatment of non-small cell lung cancer (NSCLC). However, their prognostic significance remains controversial. The present study evaluated the expression of PD-L1 and PD-1 and their potential role in an Immunoscore, supplementing the TNM classification of NSCLC. MATERIALS AND METHODS: Tissue microarrays constructed from tumor tissue samples from 2 cohorts of a total of 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC...
October 5, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27806346/cross-talk-between-microbiota-and-immune-fitness-to-steer-and-control-response-to-anti-pd-1-pdl-1-treatment
#7
REVIEW
Andrea Botticelli, Ilaria Zizzari, Federica Mazzuca, Paolo Antonio Ascierto, Lorenza Putignani, Luca Marchetti, Chiara Napoletano, Marianna Nuti, Paolo Marchetti
Immune Checkpoint Inhibitors (ICIs) are improving the survival of cancer patients, however only the 20-30% of treated patients present clinical benefits. Toxicity represents the major cause of reduced dosage, delayed drug administration and therapy discontinuation. Hence in the context of multiple treatment possibilities, the identification of predictive markers of response and toxicity is a challenging approach for drug selection in order to obtain the best clinical benefit while minimizing the side effects...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27803174/the-third-signal-cytokine-il-12-rather-than-immune-checkpoint-inhibitors-contribute-to-the-functional-restoration-of-hepatitis-d-virus-specific-t-cells
#8
Thomas Schirdewahn, Jan Grabowski, Solomon Owusu Sekyere, Birgit Bremer, Anika Wranke, Sebastian Lunemann, Verena Schlaphoff, Janina Kirschner, Svenja Hardtke, Michael Peter Manns, Markus Cornberg, Heiner Wedemeyer, Pothakamuri Venkata Suneetha
BACKGROUND:  Hepatitis D virus (HDV) infection affects 15-20 million individuals world-wide and causes severely progressive hepatitis. It is unknown to what extent cellular immune responses contribute to liver disease and control of viral replication in HDV infection. METHODS:  Immune cell frequencies and phenotypes were determined in 49 HDV-infected patients, 25 HBV-monoinfected individuals and 18 healthy controls. T-cell proliferative and cytokine-producing capacities were analysed by stimulation with overlapping peptides spanning the large HDV antigen...
October 31, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27721403/cxcl2-mif-cxcr2-signaling-promotes-the-recruitment-of-myeloid-derived-suppressor-cells-and-is-correlated-with-prognosis-in-bladder-cancer
#9
H Zhang, Y-L Ye, M-X Li, S-B Ye, W-R Huang, T-T Cai, J He, J-Y Peng, T-H Duan, J Cui, X-S Zhang, F-J Zhou, R-F Wang, J Li
The accumulation of myeloid-derived suppressor cells (MDSCs) has been observed in solid tumors and is correlated with tumor progression; however, the underlying mechanism is still poorly understood. In this study, we identified a mechanism by which tumor cells induce MDSC accumulation and expansion in the bladder cancer (BC) microenvironment via CXCL2/MIF-CXCR2 signaling. Elevated expression of CXCL2 and MIF and an increased number of CD33(+) MDSCs were detected in BC tissues, and these increases were significantly associated with advanced disease stage and poor patient prognosis (P<0...
October 10, 2016: Oncogene
https://www.readbyqxmd.com/read/27707883/protein-kinase-ck2-controls-t-cell-polarization-through-dendritic-cell-activation-in-response-to-contact-sensitizers
#10
Marie de Bourayne, Yann Gallais, Zeina El Ali, Philippe Rousseau, Marie-Hélène Damiens, Claude Cochet, Odile Filhol, Sylvie Chollet-Martin, Marc Pallardy, Saadia Kerdine-Römer
Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T-cell-mediated inflammatory skin disease caused by chemicals present in the daily or professional environment. NiSO4 and 2,4-dinitrochlorobenzene (DNCB) are 2 chemicals involved in ACD. These contact sensitizers are known to induce an up-regulation of phenotypic markers and cytokine secretion in dendritic cells (DCs; professional APCs), leading to the generation of CD8(+) Tc1/Tc17 and CD4(+) Th1/Th17 effector T cells...
October 5, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27695530/nivolumab-in-the-treatment-of-advanced-renal-cell-carcinoma-clinical-trial-evidence-and-experience
#11
REVIEW
Alessia Mennitto, Paolo Grassi, Raffaele Ratta, Elena Verzoni, Michele Prisciandaro, Giuseppe Procopio
Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α)...
October 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27522179/hedgehog-signaling-regulates-pdl-1-expression-in-cancer-cells-to-induce-anti-tumor-activity-by-activated-lymphocytes
#12
Hideya Onishi, Akiko Fujimura, Yasuhiro Oyama, Akio Yamasaki, Akira Imaizumi, Makoto Kawamoto, Mitsuo Katano, Masayo Umebayashi, Takashi Morisaki
We investigated whether hypoxia-induced activation of Hh signaling contributes to PDL-1 expression in cancer and whether it affects the anti-tumor function of activated lymphocytes. Hypoxia augmented PDL-1 expression and inhibition of Hh signaling reduced PDL-1 expression under hypoxia. When activated lymphocytes were cocultured with cancers treated with a Hh inhibitor, activated lymphocyte cell numbers increased under hypoxia. In contrast, this increase was abrogated when cancer cells were treated with a PDL-1 neutralizing antibody...
August 8, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27491654/treatment-outcome-of-pd-1-immune-checkpoint-inhibitor-in-asian-metastatic-melanoma-patients-correlative-analysis-with-pd-l1-immunohistochemistry
#13
Jinhyun Cho, Soomin Ahn, Kwai Han Yoo, Jung Han Kim, Sang-Hee Choi, Kee-Taek Jang, Jeeyun Lee
Overexpression of PD-L1 has been shown to be associated with better clinical responses to PD-1/PD-L1 blockade in melanoma. However, the utility of PD-L1 immunostaining as a predictive biomarker for anti-PD-1 treatment remains unclear, especially in melanoma of acral/mucosal origin. Materials and methods We collected and reviewed the medical records of 37 patients with metastatic melanoma who were treated with the anti-PD-1 antibodies pembrolizumab or nivolumab between January and December 2015. Patients with histologically diagnosed malignant melanoma and whose pretreatment tumor specimens were available for immunohistochemical staining of PD-L1 expression in tumor or immune cells were included...
August 4, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27485075/a-pooled-analysis-of-nivolumab-for-the-treatment-of-advanced-non-small-cell-lung-cancer-and-the-role-of-pd-l1-as-a-predictive-biomarker
#14
Pedro N Aguiar, Ilka Lopes Santoro, Hakaru Tadokoro, Gilberto de Lima Lopes, Bruno Andraus Filardi, Pedro Oliveira, Pedro Castelo-Branco, Giannis Mountzios, Ramon Andrade de Mello
BACKGROUND: Recent studies with nivolumab (a monoclonal antibody against programmed cell death 1 [PD-1] receptor) have shown promise non-small-cell lung cancer (NSCLC) treatment. METHODS: To review available clinical trials data in order to assess nivolumab efficacy and the role of tumoral PDL-1 expression as a biomarker. RESULTS: Nine eligible studies included 2102 patients. In the second line setting, nivolumab achieved a 1-year survival rate of 41%; and in the first line, a 1-year survival rate of 76%...
September 2016: Immunotherapy
https://www.readbyqxmd.com/read/27447555/activation-of-intrahepatic-cd4-cxcr5-t-and-cd19-b-cells-is-associated-with-viral-clearance-in-a-mouse-model-of-acute-hepatitis-b-virus-infection
#15
Xiao-Fei Song, Ting-Ting Hu, Yu Lei, Hu Li, Li Zhang, Miao Zhang, Bin Liu, Min Chen, Huai-Dong Hu, Hong Ren, Peng Hu
The role of immunity in the pathogenesis of acute hepatitis B virus (HBV) infection is poorly understood. The purpose of this research was to define the intrahepatic immune factors responsible for viral clearance during acute HBV infection. The model of acute HBV infection was established by hydrodynamically transfecting mice with pCDNA3.1-HBV1.3 plasmids which contained a supergenomic HBV1.3-length transgene. The frequency of CD4+ CXCR5+ T cells, CD19+ B cells and their surface molecules in livers, spleens and peripheral blood were detected using flow cytometry...
August 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27429963/resistant-mechanisms-to-braf-inhibitors-in-melanoma
#16
REVIEW
José Luís Manzano, Laura Layos, Cristina Bugés, María de Los Llanos Gil, Laia Vila, Eva Martínez-Balibrea, Anna Martínez-Cardús
Patients with advanced melanoma have traditionally had very poor prognosis. However, since 2011 better understanding of the biology and epidemiology of this disease has revolutionized its treatment, with newer therapies becoming available. These newer therapies can be classified into immunotherapy and targeted therapy. The immunotherapy arsenal includes inhibitors of CTLA4, PD-1 and PDL-1, while targeted therapy focuses on BRAF and MEK. BRAF inhibitors (vemurafenib, dabrafenib) have shown benefit in terms of overall survival (OS) compared to chemotherapy, and their combination with MEK inhibitors has recently been shown to improve progression-free survival (PFS), compared with monotherapy with BRAF inhibitors...
June 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27429658/immunotherapy-for-head-and-neck-squamous-cell-carcinoma
#17
REVIEW
Thorsten Fuereder
Over the past years immuno-oncology has evolved and become a novel promising strategy for cancer therapy. Immune checkpoint inhibitors such as pembrolizumab or nivolumab, which target the interaction between programmed death receptor 1/programmed death ligand 1 (PD-1/PDL-1) and PDL-2, have been recently approved for the treatment of various malignancies and are currently being investigated in clinical phase III trials for head and neck squamous cell carcinoma (HNSCC). Data available from these trials indicate substantial activity accompanied by a favorable safety and toxicity profile in this patient population...
2016: Memo
https://www.readbyqxmd.com/read/27232512/novel-approaches-in-cancer-immunotherapy
#18
Deepa S Subramaniam, Stephen V Liu, Giuseppe Giaccone
Our understanding of tumor immunology has exploded in the past 3 decades. The complex relationships between tumor cells, the tumor microenvironment and the immune system cells, especially the cytotoxic and helper T cells and the regulatory T cells are beginning to be elucidated. In this review, we will attempt to provide a brief primer of tumor immunology. Cytokine therapy has historically been the mainstay of immunotherapy in cancers such as melanoma and kidney cancer. We will review some of the advances made with cancer vaccines, with a focus on peptide vaccines, tumor cell vaccines and immune cell vaccines...
April 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27224873/programmed-death-1-immune-checkpoint-blockade-in-the-treatment-of-hematological-malignancies
#19
Panagiotis Tsirigotis, Bipin N Savani, Arnon Nagler
The use of tumor-specific monoclonal antibodies (MAbs) has revolutionize the field of cancer immunotherapy. Although treatment of malignant diseases with MAbs is promising, many patients fail to respond or relapse after an initial response. Both solid tumors and hematological malignancies develop mechanisms that enable them to evade the host immune system by usurping immune checkpoint pathways such as PD-1, PD-2, PDL-1, or PDL-2 (programmed cell death protein-1 or 2 and PD-Ligand 1 or 2), which are expressed on activated T cells and on T-regulatory, B cells, natural killers, monocytes, and dendritic cells...
September 2016: Annals of Medicine
https://www.readbyqxmd.com/read/27200491/can-immunostimulatory-agents-enhance-the-abscopal-effect-of-radiotherapy
#20
REVIEW
Antonin Levy, Cyrus Chargari, Aurelien Marabelle, Jean-Luc Perfettini, Nicolas Magné, Eric Deutsch
Ionising radiation (IR) may harm cancer cells through a rare indirect out-of-field phenomenon described as the abscopal effect. Increasing evidence demonstrates that radiotherapy could be capable of generating tumour-specific immune responses. On the other hand, effects of IR also include inhibitory immune signals on the tumour microenvironment. Following these observations, and in the context of newly available immunostimulatory agents in metastatic cancers (anti-cytotoxic T lymphocyte-associated antigen 4 and programmed cell death protein-1 or -ligand 1 [PD1 or PDL-1]), there is a remarkable potential for synergistic combinations of IR with such agents that act through the reactivation of immune surveillance...
July 2016: European Journal of Cancer
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