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Clémence Granier, Emeline Vinatier, Elia Colin, Marion Mandavit, Charles Dariane, Virginie Verkarre, Lucie Biard, Rami El Zein, Corinne Lesaffre, Isabelle Galy-Fauroux, Hélène Roussel, Eléonore De Guillebon, Charlotte Blanc, Antonin Saldmann, Cécile Badoual, Alain Gey, Éric Tartour
Immune cells are important components of the tumor microenvironment and influence tumor growth and evolution at all stages of carcinogenesis. Notably, it is now well established that the immune infiltrate in human tumors can correlate with prognosis and response to therapy. The analysis of the immune infiltrate in the tumor microenvironment has become a major challenge for the classification of patients and the response to treatment. The co-expression of inhibitory receptors such as Program Cell Death Protein 1 (PD1; also known as CD279), Cytotoxic T Lymphocyte Associated Protein 4 (CTLA-4), T-Cell Immunoglobulin and Mucin Containing Protein-3 (Tim-3; also known as CD366), and Lymphocyte Activation Gene 3 (Lag-3; also known as CD223), is a hallmark of T cell exhaustion...
February 8, 2018: Journal of Visualized Experiments: JoVE
Mireille Laforge, Ricardo Silvestre, Vasco Rodrigues, Julie Garibal, Laure Campillo-Gimenez, Shahul Mouhamad, Valérie Monceaux, Marie-Christine Cumont, Henintsoa Rabezanahary, Alain Pruvost, Anabela Cordeiro-da-Silva, Bruno Hurtrel, Guido Silvestri, Anna Senik, Jérôme Estaquier
Apoptosis has been proposed as a key mechanism responsible for CD4+ T cell depletion and immune dysfunction during HIV infection. We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV-infected rhesus macaques (RMs). When administered during the acute phase of infection, Q-VD-OPH was associated with (a) reduced levels of T cell death, (b) preservation of CD4+/CD8+ T cell ratio in lymphoid organs and in the gut, (c) maintenance of memory CD4+ T cells, and (d) increased specific CD4+ T cell response associated with the expression of cytotoxic molecules...
March 19, 2018: Journal of Clinical Investigation
Aisha Nazli, Sara Dizzell, Muhammad Atif Zahoor, Victor H Ferreira, Jessica Kafka, Matthew William Woods, Michel Ouellet, Ali A Ashkar, Michel J Tremblay, Dawn Me Bowdish, Charu Kaushic
More than 40% of HIV infections occur via female reproductive tract (FRT) through heterosexual transmission. Epithelial cells that line the female genital mucosa are the first line of defense against HIV-1 and other sexually transmitted pathogens. These sentient cells recognize and respond to external stimuli by induction of a range of carefully balanced innate immune responses. Previously, we have shown that in response to HIV-1 gp120, the genital epithelial cells (GECs) from upper reproductive tract induce an inflammatory response that may facilitate HIV-1 translocation and infection...
March 19, 2018: Cellular & Molecular Immunology
Kirstin Harling, Ernest Adankwah, Alptekin Güler, Anthony Afum-Adjei Awuah, Louis Adu-Amoah, Ertan Mayatepek, Ellis Owusu-Dabo, Norman Nausch, Marc Jacobsen
T-cells critically contribute to protection against Mycobacterium tuberculosis infection, and impaired T-cell responses can lead to disease progression. Pro-inflammatory and immunosuppressive cytokines affect T-cells, and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function. Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases...
March 19, 2018: Cellular & Molecular Immunology
Shimpei Kawamoto
No abstract text is available yet for this article.
2018: Arerugī, [Allergy]
Tomotaka Kawayama, Takashi Kinoshita, Kazuko Matsunaga, Yoshiko Naito, Jun Sasaki, Yoshikazu Tominaga, Tomoaki Hoshino
Asthma is an allergic disease characterized by chronic airway inflammation, airway hyperresponsiveness (AHR), reversibility and remodeling. Inhaled corticosteroids (ICS) are effective in many patients with asthma. However, ICS are a controlling, but not but curative treatment, and there are still many patients with refractory and difficult-to-treat asthma. The evaluation of airway inflammation by induced sputum, non-specific AHR by methacholine, and asthmatic reactions by specific allergen challenge techniques are useful not only to investigate the pathogenesis of asthma but also to help develop new drugs for asthma management...
March 16, 2018: Kurume Medical Journal
Jale Moradi, Maryam Izad, Mina Tabrizi, Nader Mosavari, Behnaz Esmaeili, Mohammad Mehdi Feizabadi
One third of the world population are latently infected with Mycobacterium tuberculosis and are at the risk of reactivation of tuberculosis (TB). The most effective strategy for control of TB worldwide is the development of a vaccine that inhibits progression of latent TB to active infection. In this study, two optimized constructs consisting of multi-epitopes DNA derived from three latency antigens Rv2029c, Rv2031c, and Rv2627c fused with or without light chain 3 (LC3) are synthetized. The immunogenicity effectiveness of two DNA constructs was evaluated in the mouse model...
March 19, 2018: Acta Microbiologica et Immunologica Hungarica
E Ridolo, I Martignago, S Masieri
Allergic Rhinitis (AR) is an IgE-mediated hypersensitivity disease caused by inhalation of an allergen to which the patients is sensitized. Etiopathogenesis of AR comprises a sensitization phase, an immediate phase and a late phase. In the sensitization phase, inhaled allergens are processed in peptides and come into contact with the nasal mucosa cells. Antigen-Presenting Cells (APCs), especially represented by Dendritic Cells (DCs), capture them through the interaction with their own MHC class II complexes and migrate to lymph nodes...
January 2018: Journal of Biological Regulators and Homeostatic Agents
Zhongzhen Yi, Brooke L Prinzing, Felicia Cao, Stephen Gottschalk, Giedre Krenciute
Glioblastoma is the most aggressive primary brain tumor in humans and is virtually incurable with conventional therapies. Chimeric antigen receptor (CAR) T cell therapy targeting the glioblastoma antigen EphA2 is an attractive approach to improve outcomes because EphA2 is expressed highly in glioblastoma but only at low levels in normal brain tissue. Building upon our previous findings in this area, we generated and evaluated a panel of EphA2-specific CARs. We demonstrate here that T cells expressing CD28...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Michael C Milone, Vijay G Bhoj
Adoptive cellular therapy using T cells with tumor specificity derived from either natural T cell receptors (TCRs) or an artificial chimeric antigen receptor (CAR) has reached late phase clinical testing, with two CAR T cell therapies achieving regulatory approval within the United States in 2017. The effective use of these therapies depends upon an understanding of their pharmacology, which is quite divergent from traditional small molecule or biologic drugs. We review the different types of T cell therapy under clinical development, the factors affecting cellular kinetics following infusion, and the relationship between these cellular kinetics and anti-cancer activity...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
Henrieta Fraser, Niloufar Safinia, Nathali Grageda, Sarah Thirkell, Katie Lowe, Laura J Fry, Cristiano Scottá, Andrew Hope, Christopher Fisher, Rachel Hilton, David Game, Paul Harden, Andrew Bushell, Kathryn Wood, Robert I Lechler, Giovanna Lombardi
The concept of regulatory T cell (Treg)-based immunotherapy has enormous potential for facilitating tolerance in autoimmunity and transplantation. Clinical translation of Treg cell therapy requires production processes that satisfy the rigors of Good Manufacturing Practice (GMP) standards. In this regard, we report our findings on the implementation of a robust GMP compliant process for the ex vivo expansion of clinical grade Tregs, demonstrating the feasibility of this developed process for the manufacture of a final product for clinical application...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
Purva V Sharma, Michael Witteman, Swethika Sundaravel, Tulisa Larocca, Yuanming Zhang, Harry Goldsztajn
Adult T cell lymphoma (ATL), is a peripheral T cell neoplasm associated with infection by human T-lymphotropic virus (HTLV). This is a case of a 28-year-old lady who presented with back pain for the past month and recent onset weakness in her lower extremities bilaterally. She has a history of T-cell lymphoma secondary to HTLV-1 under remission since 2014 and systemic lupus erythematosus complicated by lupus nephritis. On physical examination patient had hyper-reflexia in both knees, ankle clonus bilaterally and spasticity in both her lower extremities...
February 2018: Intractable & Rare Diseases Research
Mamatha Siricilla, Lydia Irwin, Andres Ferber
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of nonclassical Hodgkin lymphoma (HL). It resembles non-Hodgkin lymphoma (NHL), by expressing classic B cell markers such as CD20 and CD79a however lacks definitive HL markers (such as CD15 and CD30). T cell histiocyte-rich large B cell lymphoma (THRLBCL), on the other hand, is a distinct entity classified under NHL and considered a variant of diffuse large B cell lymphoma (DLBCL). NLPHL can look morphologically and immunologically similar to THRLBCL and often poses a diagnostic challenge...
2018: Case Reports in Oncological Medicine
Behdod Poushanchi, Hiren Vallabh, Gorman Joel Reynolds
Ipilimumab is a monoclonal antibody that works as an immunotherapeutic agent through selective targeting of T cells to strengthen the response to metastatic melanoma. It is well known that this pharmaceutical agent can cause the adverse effect of colitis. We report a rare presentation of ileocolitis refractory to both glucocorticosteroids and infliximab with a resultant pneumatosis and perforation requiring subtotal colectomy and end ileostomy.
2018: Case Reports in Gastrointestinal Medicine
Selvi Jegatheeson, Julie Wayne, Laura K Brockley
Case summary: A 7-year-old male neutered domestic shorthair cat presented for investigation of a swelling over the right forelimb. Radiographs of the right forelimb revealed significant lysis and soft tissue swelling surrounding a previously implanted surgical plate, used to repair a fracture of the distal radius 5 years prior. The implant was removed, and a biopsy was collected. Histopathological analysis and immunohistochemistry diagnosed a non-epitheliotropic T-cell cutaneous lymphoma...
January 2018: JFMS Open Reports
Weili Wang, Kuansong Wang, Zihua Chen, Ling Chen, Wei Guo, Ping Liao, Daniel Rotroff, Todd C Knepper, Zhaoqian Liu, Wei Zhang, Howard L Mcleod, Yijing He
Background: Gastric cancer (GC) is a major cause of cancer deaths, especially in Eastern Asia. Current classification systems, including the WHO, Lauren, and TCGA, have clarified the pathological and molecular profiles of GC. However, these classifications lack an association with clinical outcome and guidance for medication selection. Objective: We aimed to identify a new immunoclassification for GC to better predict patient prognosis and aid in patient selection for immunotherapy...
February 23, 2018: Oncotarget
Heqiang Sun, Hanmei Yuan, Ranjing Tan, Bin Li, Gang Guo, Jinyong Zhang, Haiming Jing, Yi Qin, Zhuo Zhao, Quanming Zou, Chao Wu
Helicobacter pylori has infected more than half of the world's population, causing gastritis, gastric ulcers, gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer. The oral recombinant Helicobacter pylori vaccine currently used has made great progress in addressing this problem, however, its efficacy and longevity still need to be improved. Th1 and Th17 cells play essential roles in local protection against Helicobacter pylori in the stomach mucosa. Additionally, protective immunodominant antigens are the preferred for a vaccine...
February 23, 2018: Oncotarget
Wei Tian, Jun Ma, Ruyi Shi, Chongren Ren, Jiefeng He, Haoliang Zhao
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. γδ T cells have been revealed to be promising candidates for immunotherapy in patients with HCC. However, the use of these cells in clinical practice has been demonstrated to be challenging. In the present study, γδ T cells isolated from the peripheral blood of patients with HCC (n=83) and healthy donors (n=15) were characterized. Flow cytometry was used to analyze the proportion, phenotype, tumor-killing capacity and cytokine secretion of regulatory T cells (Tregs) and γδ T17 cells in peripheral blood samples prior to and following amplification...
April 2018: Oncology Letters
Zilong Hu, Shidong Hu, Youjun Wu, Songyan Li, Changzheng He, Xiaowei Xing, Yufeng Wang, Xiaohui Du
Although adoptive cell therapy (ACT) has demonstrated effective and remarkable clinical responses in several studies, this approach does not lead to objective clinical responses in all cases. The function of ACT is often compromised by various tumor escape mechanisms, including the accumulation of immunoregulatory cells. As a result of peritoneal metastasis in the terminal stage, malignant ascites fluid lacks effectiveness and is a poor prognostic factor for gastric cancer. The present study assessed T-cell subsets in lymphocytes derived from malignant ascites, and investigated the effects of arsenic trioxide (As2 O3 ) on regulatory T cells (Tregs) and ascites-derived tumor-infiltrating lymphocytes (TILs) in vitro ...
April 2018: Oncology Letters
Zilong Hu, Yue Ma, Zhiyang Shang, Shidong Hu, Kai Liang, Wentao Liang, Xiaowei Xing, Yufeng Wang, Xiaohui Du
Monoclonal antibodies recognizing programmed death-ligand 1 (PD-L1) have been used for the clinical treatment of diverse tumor types as a form of immune checkpoint inhibitor, with a favorable therapeutic effect. Dendritic cells (DCs) are potent antigen-presenting cells that serve a pivotal role in the activation of T cells, particularly cytotoxic T lymphocytes (CTLs). DC vaccines loaded with tumor antigens, DC-CTLs and activated T cells have been revealed to be a safe and effective treatment approach against colorectal cancer within a clinical setting...
April 2018: Oncology Letters
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