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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
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
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
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
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
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
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...
July 18, 2016: Oncotarget
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
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
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
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...
May 25, 2016: Annals of Medicine
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
Marco Puzzoni, Nicola Silvestris, Francesco Leone, Riccardo Giampieri, Luca Faloppi, Laura Demurtas, Emanuela Dell'Aquila, Donatella Marino, Oronzo Brunetti, Silvio Ken Garattini, Elena Ongaro, Giorgio Astara, Laura Orgiano, Giuseppe Aprile, Daniele Santini, Mario Scartozzi
The encouraging results in immunotherapy for melanoma also led the way for translational and clinical research about immune-related mechanisms possibly relevant for gastrointestinal tumours. It is in fact now evident that the immune checkpoint modulation and in particular cell-mediated immune-response through programmed cell death-1 (PD-1) and the cytotoxic T-lymphocyte antigen-4 (CTLA4) receptors along with the regulatory T cells activity all have a relevant role in gastrointestinal cancers as well. This review aims to explore the state of the art of immunotherapy for gastrointestinal tumours, deepening recent scientific evidence regarding anti PD-1/PDL-1 and anti CTLA4 monoclonal antibodies, peptide based vaccine, DNA based vaccine, and pulsed dendritic cells, either alone or in combination with other antineoplastic medical therapy and locoregional treatments...
May 17, 2016: Targeted Oncology
François-Xavier Danlos, Cécile Pagès, Barouyr Baroudjian, Laetitia Vercellino, Maxime Battistella, Maurice Mimoun, Majdi Jebali, Martine Bagot, Abdellatif Tazi, Céleste Lebbé
To our knowledge, we report the first case of sarcoid-like granulomatous reaction induced by nivolumab, a fully human IgG4 anti-programmed death 1 (PD-1) immune checkpoint inhibitor antibody. A 57-year-old man was treated with nivolumab 3 mg/kg for 2 weeks for a desmoplastic melanoma stage III American Joint Commission on Cancer, with no BRAF, NRAS, and cKit mutations. At 10 months, although melanoma complete response was achieved, he developed sarcoid-like granulomatous reaction in the mediastinal lymph node and skin, which resumed after nivolumab arrest...
May 2016: Chest
Katherine L Crossland, Mario Abinun, Peter D Arkwright, Timothy D Cheetham, Simon H Pearce, Catharien M U Hilkens, Desa Lilic
Loss-of-function mutations of the Autoimmune Regulator (AIRE) gene results in organ-specific autoimmunity and disease Autoimmune Polyendocrinopathy type 1 (APS1)/Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED). The AIRE protein is crucial in the induction of central tolerance, promoting ectopic expression of tissue-specific antigens in medullary thymic epithelial cells and enabling removal of self-reactive T-cells. AIRE expression has recently been detected in myeloid dendritic cells (DC), suggesting AIRE may have a significant role in peripheral tolerance...
June 2016: Autoimmunity
Peggy P Ho, Lawrence Steinman
Bile acids are ligands for the nuclear hormone receptor, farnesoid X receptor (FXR). The bile acid-FXR interaction regulates bile acid synthesis, transport, and cholesterol metabolism. Recently, bile acid-FXR regulation has been reported to play an integral role in both hepatic and intestinal inflammation, and in atherosclerosis. In this study, we found that FXR knockout mice had more disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Obeticholic acid (6α-ethyl-chenodeoxycholic acid, 6-ECDCA), a synthetic FXR agonist, is an orally available drug that is currently in clinical trials for the treatment of inflammatory diseases such as alcoholic hepatitis, nonalcoholic steatohepatitis, and primary biliary cirrhosis...
February 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
Dharmendra Singh, Chandan Kumar Singh, Ram Sewak Singh Tomar, Jyoti Taunk, Ranjeet Singh, Sadhana Maurya, Ashish Kumar Chaturvedi, Madan Pal, Rajendra Singh, Sarawan Kumar Dubey
The success of drought tolerance breeding programs can be enhanced through molecular assortment of germplasm. This study was designed to characterize molecular diversity within and between Lens species with different adaptations to drought stress conditions using SSR markers. Drought stress was applied at seedling stage to study the effects on morpho-physiological traits under controlled condition, where tolerant cultivars and wilds showed 12.8-27.6% and 9.5-23.2% reduction in seed yield per plant respectively...
2016: PloS One
Ross A Soo
Immune checkpoint inhibition targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a very promising therapeutic avenue in the treatment of patients with advanced stage non-small cell lung cancer but only a subset of patients derives clinical benefit from PD-1/PD-L1 inhibitors. Studies to date have reported patients with PDL-1 expressing tumors have a better outcome than those with PDL-1 negative tumors but assays used to identify PD-L1 positive patients has been challenging...
December 2015: Translational Lung Cancer Research
Emanuela Rossi, Assunta Sgambato, Giovanni De Chiara, Francesca Casaluce, Tania Losanno, Paola Claudia Sacco, Giuseppe Santabarbara, Cesare Gridelli
The advent of immunotherapy has recently expanded the therapeutic options in advanced non-small cell lung cancer (NSCLC). In these patients, the recent efficacy demonstration of antibodies against immune checkpoints: the anti-programmed death-1 (PD-1) and anti-programmed death ligand-1 (PD-L1), has led to approval of nivolumab and pembrolizumab (anti-PD-1) in the treatment of advanced NSCLC. The mechanism of action of checkpoint inhibitors explains the development of autoimmune diseases as a side-effect of these medications...
2016: Expert Review of Clinical Pharmacology
Johan A Carlsson, Agnes E Wold, Ann-Sofie Sandberg, Sofia M Östman
Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures...
2015: PloS One
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