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Joana Felix, Jérome Lambert, Marie Roelens, Eve Maubec, Hélène Guermouche, Cécile Pages, Irina Sidina, Debora J Cordeiro, Guitta Maki, François Chasset, Raphaël Porcher, Martine Bagot, Anne Caignard, Antoine Toubert, Céleste Lebbé, Hélène Moins-Teisserenc
PURPOSE: Therapy targeting CTLA-4 immune checkpoint provides increased survival in patients with advanced melanoma. However, immunotherapy is frequently associated with delayed and heterogeneous clinical responses and it is important to identify prognostic immunological correlates of clinical endpoints. EXPERIMENTAL DESIGN: 77 patients with stage III/IV melanoma were treated with ipilimumab alone every 3 weeks, during 9 weeks. Blood samples were collected at the baseline and before each dose for in depth immune monitoring...
July 2016: Oncoimmunology
Florin Tuluc, Sergei Spitsin, Nancy B Tustin, Jennifer B Murray, Richard Tustin, Laura A Schankel, Andrew Wiznia, Sharon Nachman, Steven D Douglas
We investigated the effect of combination antiretroviral therapy (cART) on immune recovery, particularly on the percentages of PD-1-positive cells within the major leukocyte subsets. Cryopreserved peripheral blood mononuclear cells and plasma samples collected longitudinally from a subset of 13 children and adolescents (between 9.7 and 18.2 years old) who were enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1066 were used for this study. Immunophenotyping by flow cytometry was performed to determine the effect of raltegravir-containing cART regimen on the distribution of leukocyte populations, on the expression of PD-1 on T cell subpopulations, and on the expression of well-established markers of T cell activation (CD38 and HLA-DR) on CD8 T cells...
October 18, 2016: AIDS Research and Human Retroviruses
Alexandre Morrot
No abstract text is available yet for this article.
June 2016: Annals of Translational Medicine
Francesca Calascibetta, Luca Micci, Diane Carnathan, Benton Lawson, Thomas H Vanderford, Steven E Bosinger, Kirk Easley, Ann Chahroudi, Joseph Mackel, Brandon F Keele, Samuel Long, Jeffrey Lifson, Mirko Paiardini, Guido Silvestri
UNLABELLED: Simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) do not develop AIDS despite high levels of viremia. Key factors involved in the benign course of SIV infection in SMs are the absence of chronic immune activation and low levels of infection of CD4(+) central memory (TCM) and stem cell memory (TSCM) T cells. To better understand the role of virus replication in determining the main features of SIV infection in SMs, we treated 12 SMs with a potent antiretroviral therapy (ART) regimen for 2 to 12 months...
August 15, 2016: Journal of Virology
Hai Hong, Yong Gu, Si Yuan Sheng, Chuan Gang Lu, Jian Yong Zou, Chang You Wu
Human stem cell-like memory T (Tscm) cells are long-lived, self-renewing memory lymphocytes that can differentiate into effector cells and mediate strong antitumour response in murine model. The distribution and function of Tscm cells in human lung cancer remain unknown. In this study, we investigated the properties of human Tscm cells in the blood and lymph node of non-small cell lung cancer (NSCLC) patients. There were more CD4 Tscm cells in blood from NSCLC patients than from healthy donors, fewer CD4 and CD8 TSCM cells in blood than in lymph node from NSCLC patients...
July 2016: Journal of Immunotherapy
Marianna Sabatino, Jinhui Hu, Michele Sommariva, Sanjivan Gautam, Vicki Fellowes, James D Hocker, Sean Dougherty, Haiying Qin, Christopher A Klebanoff, Terry J Fry, Ronald E Gress, James N Kochenderfer, David F Stroncek, Yun Ji, Luca Gattinoni
Long-lived, self-renewing, multipotent T memory stem cells (TSCM) can trigger profound and sustained tumor regression but their rareness poses a major hurdle to their clinical application. Presently, clinically compliant procedures to generate relevant numbers of this T-cell population are undefined. Here, we provide a strategy for deriving large numbers of clinical-grade tumor-redirected TSCM starting from naive precursors. CD8(+)CD62L(+)CD45RA(+) naive T cells enriched by streptamer-based serial-positive selection were activated by CD3/CD28 engagement in the presence of interleukin-7 (IL-7), IL-21, and the glycogen synthase-3β inhibitor TWS119, and genetically engineered to express a CD19-specific chimeric antigen receptor (CD19-CAR)...
July 28, 2016: Blood
Emily K Cartwright, David Palesch, Maud Mavigner, Mirko Paiardini, Ann Chahroudi, Guido Silvestri
UNLABELLED: Treatment of human immunodeficiency virus (HIV) infection with antiretroviral therapy (ART) has significantly improved prognosis. Unfortunately, interruption of ART almost invariably results in viral rebound, attributed to a pool of long-lived, latently infected cells. Based on their longevity and proliferative potential, CD4(+) T memory stem cells (TSCM) have been proposed as an important site of HIV persistence. In a previous study, we found that in simian immunodeficiency virus (SIV)-infected rhesus macaques (RM), CD4(+) TSCM are preserved in number but show (i) a decrease in the frequency of CCR5(+) cells, (ii) an expansion of the fraction of proliferating Ki-67(+) cells, and (iii) high levels of SIV DNA...
August 1, 2016: Journal of Virology
Godehard Scholz, Camilla Jandus, Lianjun Zhang, Camille Grandclément, Isabel C Lopez-Mejia, Charlotte Soneson, Mauro Delorenzi, Lluis Fajas, Werner Held, Olivier Dormond, Pedro Romero
Robust, long-lasting immune responses are elicited by memory T cells that possess properties of stem cells, enabling them to persist long-term and to permanently replenish the effector pools. Thus, stem cell-like memory T (TSCM) cells are of key therapeutic value and efforts are underway to characterize TSCM cells and to identify means for their targeted induction. Here, we show that inhibition of mechanistic/mammalian Target of Rapamycin (mTOR) complex 1 (mTORC1) by rapamycin or the Wnt-β-catenin signalling activator TWS119 in activated human naive T cells leads to the induction of TSCM cells...
February 2016: EBioMedicine
Kohei Hosokawa, Pawel Muranski, Xingmin Feng, Danielle M Townsley, Baoying Liu, Jared Knickelbein, Keyvan Keyvanfar, Bogdan Dumitriu, Sawa Ito, Sachiko Kajigaya, James G Taylor, Mariana J Kaplan, Robert B Nussenblatt, A John Barrett, John O'Shea, Neal S Young
Memory stem T cells (TSCMs) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. Hallmarks of autoimmune disease pathogenesis are abnormal CD4(+) and CD8(+) T cell activation. We investigated the TSCM subset in 55, 34, 43, and 5 patients with acquired aplastic anemia (AA), autoimmune uveitis, systemic lupus erythematosus, and sickle cell disease, respectively, as well as in 41 age-matched healthy controls. CD8(+) TSCM frequency was significantly increased in AA compared with healthy controls...
February 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Giacomo Oliveira, Eliana Ruggiero, Maria Teresa Lupo Stanghellini, Nicoletta Cieri, Mattia D'Agostino, Mattio D'Agostino, Raffaele Fronza, Christina Lulay, Francesca Dionisio, Sara Mastaglio, Raffaella Greco, Jacopo Peccatori, Alessandro Aiuti, Alessandro Ambrosi, Luca Biasco, Attilio Bondanza, Antonio Lambiase, Catia Traversari, Luca Vago, Christof von Kalle, Manfred Schmidt, Claudio Bordignon, Fabio Ciceri, Chiara Bonini
Long-lasting immune protection from pathogens and cancer requires the generation of memory T cells able to survive long-term. To unravel the immunological requirements for long-term persistence of human memory T cells, we characterized and traced, over several years, T lymphocytes genetically modified to express the thymidine kinase (TK) suicide gene that were infused in 10 patients after haploidentical hematopoietic stem cell transplantation (HSCT). At 2 to 14 years after infusion and in the presence of a broad and resting immune system, we could still detect effectors/effector memory (TEM/EFF), central memory (TCM), and stem memory (TSCM) TK(+) cells, circulating at low but stable levels in all patients...
December 9, 2015: Science Translational Medicine
Chongsheng Qian, Yingying Wang, Huili Cai, Caroline Laroye, Marcelo De Carvalho Bittencourt, Laurence Clement, Jean-François Stoltz, Véronique Decot, Loïc Reppel, Danièle Bensoussan
Adoptive antiviral cellular immunotherapy by infusion of virus-specific T cells (VSTs) is becoming an alternative treatment for viral infection after hematopoietic stem cell transplantation. The T memory stem cell (TSCM) subset was recently described as exhibiting self-renewal and multipotency properties which are required for sustained efficacy in vivo. We wondered if such a crucial subset for immunotherapy was present in VSTs. We identified, by flow cytometry, TSCM in adenovirus (ADV)-specific interferon (IFN)-γ+ T cells before and after IFN-γ-based immunomagnetic selection, and analyzed the distribution of the main T-cell subsets in VSTs: naive T cells (TN), TSCM, T central memory cells (TCM), T effector memory cell (TEM), and effector T cells (TEFF)...
January 2016: Journal of Immunotherapy
Jacqueline K Flynn, Paul R Gorry
T memory stem cells (TSCM) are the earliest developmental stage of memory T cells, displaying stem cell-like properties and exhibiting a gene profile between naive and central memory (CM) T cells. Their long-lifespan, robust proliferative potential and self-renewal capacity has generated much research and clinical interest particularly for therapeutic use. Here, we discuss recent findings published in Science Translational Medicine by Biasco and colleagues [2015 Feb 4;7(273):273ra13], which provided evidence for the persistence of TSCM in humans for up to 12 years after infusion of genetically modified lymphocytes, and we examine the implications for the development of novel immunotherapies using TSCM...
October 2015: Annals of Translational Medicine
Anne C H Goh, Stephanie Wong, Jonathan G Zaroff, Navid Shafaee, Robert J Lundstrom
PURPOSE: To determine whether anxiety or depression is associated with takotsubo stress cardiomyopathy (TSCM). METHODS: A retrospective case-control study was conducted among 73 TSCM cases and 111 acute coronary syndrome (ACS) controls matched for age, sex, and cardiac catheterization date. The study was conducted between May 1, 2009, and February 28, 2010. The Hospital Anxiety and Depression Scale was completed by all participants after hospital discharge. The Hospital Anxiety and Depression Scale was used to assess psychological distress with measurement of anxiety and depression scores...
March 2016: Journal of Cardiopulmonary Rehabilitation and Prevention
Ling Xu, Yikai Zhang, Gengxin Luo, Yangqiu Li
Adoptive cell therapy (ACT) is rapidly migrating from bench to clinical therapy for hematological malignancies. Recently, a new subtype of memory T cells, stem cell memory T (TSCM) cells, was shown to be one of the most favorable subsets for ACT. TSCM has high self-renewal capacity and is associated with superior T cell engraftment, persistence, and antitumor immunity. In this review, we focused on the characteristics of antigen-specific TSCM cells and discussed their potential for immunotherapy targeting hematological malignancies...
2015: Journal of Hematology & Oncology
Selena Vigano, Jordi Negron, Zhengyu Ouyang, Eric S Rosenberg, Bruce D Walker, Mathias Lichterfeld, Xu G Yu
UNLABELLED: HIV-1-specific CD8 T cells can influence HIV-1 disease progression during untreated HIV-1 infection, but the functional and phenotypic properties of HIV-1-specific CD8 T cells in individuals treated with suppressive antiretroviral therapy remain less well understood. Here we show that a subgroup of HIV-1-specific CD8 T cells with stem cell-like properties, termed T memory stem cells (TSCM cells), is enriched in patients receiving suppressive antiretroviral therapy compared with their levels in untreated progressors or controllers...
August 2015: Journal of Virology
Masaru Takeshita, Katsuya Suzuki, Yoshiaki Kassai, Maiko Takiguchi, Yusuke Nakayama, Yuki Otomo, Rimpei Morita, Takahiro Miyazaki, Akihiko Yoshimura, Tsutomu Takeuchi
T cells are considered to develop through three stages, from naïve T (Tn) into central memory T (Tcm) and finally into effector memory T (Tem). Among the subsets of Tn, stem cell memory T (Tscm) were recently found to be the least developed memory subset. While this subset was revealed to possess self-reproducibility and multipotentiality, little is known about the relationship between development and polarity. We conducted transcriptome analysis of human CD4(+) T subsets and found that Tscm was a clearly distinct subset, located between Tn and Tcm...
July 2015: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Michael Schmueck-Henneresse, Radwa Sharaf, Katrin Vogt, Benjamin J D Weist, Sybille Landwehr-Kenzel, Henrike Fuehrer, Anke Jurisch, Nina Babel, Cliona M Rooney, Petra Reinke, Hans-Dieter Volk
Memory T cells expressing stem cell-like properties have been described recently. The capacity of self-renewal and differentiation into various memory/effector subsets make them attractive for adoptive T cell therapy to combat severe virus infections and tumors. The very few reports on human memory stem T cells (T(SCM)) are restricted to analyses on polyclonal T cells, but extensive data on Ag-specific T(SCM )are missing. This might be due to their very low frequency limiting their enrichment and characterization...
June 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Chunfang Zhao, Idania Marrero, Aditi Narsale, Rosita Moya, Joanna D Davies
CD4(+) CD44(v.low) cells are peripheral precursor T cells that inhibit lymphopenia by generating a large CD4(+) T cell pool containing balanced numbers of naïve, memory, and regulatory Foxp3(+) cells with a diverse TCR repertoire. Recent thymic emigrants (RTE) and stem cell-like memory T cells (T(SCM)) can also replenish a T cell pool. In this study we formally test whether CD44(v.low) cells are the same population as RTE and T(SCM). Our data show that, in contrast to RTE, CD44(v.low) cells express high levels of CD45RB and low levels of CD24...
August 2015: Cellular Immunology
Silvia A Fuertes Marraco, Charlotte Soneson, Laurène Cagnon, Philippe O Gannon, Mathilde Allard, Samia Abed Maillard, Nicole Montandon, Nathalie Rufer, Sophie Waldvogel, Mauro Delorenzi, Daniel E Speiser
Efficient and persisting immune memory is essential for long-term protection from infectious and malignant diseases. The yellow fever (YF) vaccine is a live attenuated virus that mediates lifelong protection, with recent studies showing that the CD8(+) T cell response is particularly robust. Yet, limited data exist regarding the long-term CD8(+) T cell response, with no studies beyond 5 years after vaccination. We investigated 41 vaccinees, spanning 0.27 to 35 years after vaccination. YF-specific CD8(+) T cells were readily detected in almost all donors (38 of 41), with frequencies decreasing with time...
April 8, 2015: Science Translational Medicine
Yuya Nagai, Masahiro Kawahara, Masakatsu Hishizawa, Yayoi Shimazu, Noriko Sugino, Sumie Fujii, Norimitsu Kadowaki, Akifumi Takaori-Kondo
Adult T-cell leukemia (ATL) is a peripheral CD4(+) T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). Despite several investigations using human specimens and mice models, the exact origin of ATL cells remains unclear. Here we provide a new insight into the hierarchical architecture of ATL cells. HTLV-1-infected cells and dominant ATL clones are successfully traced back to CD45RA(+) T memory stem (TSCM) cells, which were recently identified as a unique population with stemlike properties, despite the fact that the majority of ATL cells are CD45RA(-)CD45RO(+) conventional memory T cells...
June 4, 2015: Blood
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