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https://www.readbyqxmd.com/read/30321596/immune-reconstitution-and-infection-patterns-following-early-alemtuzumab-and-reduced-intensity-transplantation-for-non-malignant-disorders-in-pediatric-patients
#1
Sima T Bhatt, Jeffrey J Bednarski, Julia Berg, Kathryn Trinkaus, Lisa Murray, Robert Hayashi, Ginny Schulz, Monica Hente, Michael Grimley, Ka Wah Chan, Naynesh Kamani, David Jacobsohn, Michael Nieder, Gregory Hale, Lolie Yu, Roberta Adams, Jignesh Dalal, Michael A Pulsipher, Paul Haut, Sonali Chaudhury, Jeffrey Davis, Jennifer Jaroscak, Martin Andreansky, Jennifer Willert, Shalini Shenoy
Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for many nonmalignant disorders (NMD) and is curative or prevents disease progression. Reduced intensity conditioning (RIC) in HSCT for NMD may reduce regimen-related acute toxicities and late complications. Myeloablation is often replaced by immune suppression in RIC regimens to support donor engraftment. The pace of immune reconstitution following immune suppression by RIC regimens is influenced by agents used, donor source, and graft-versus-host disease (GVHD) prophylaxis/treatment...
October 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/30320884/the-regulatory-roles-of-glycosphingolipid-enriched-lipid-rafts-in-immune-systems
#2
REVIEW
Hitoshi Nakayama, Masakazu Nagafuku, Akemi Suzuki, Kazuhisa Iwabuchi, Jin-Ichi Inokuchi
Lipid rafts formed by glycosphingolipids on cellular membranes play important roles in innate and adaptive immunity. Lactosylceramide (LacCer) forms lipid rafts on plasma and granular membranes of human neutrophils. These LacCer-enriched lipid rafts bind directly to pathogenic components, such as pathogenic fungi-derived β-glucan and Mycobacteria-derived lipoarabinomannan via carbohydrate-carbohydrate interactions, and mediate innate immune responses to these pathogens. In contrast, a-series and o-series gangliosides form distinct rafts on CD4+ and CD8+ T cell subsets, respectively, contributing to the respective functions of these cells and stimulating adaptive immune responses through T cell receptors...
October 15, 2018: FEBS Letters
https://www.readbyqxmd.com/read/30320878/during-acute-graft-versus-host-disease-cd28-deletion-in-donor-cd8-but-not-cd4-t-cells-maintains-anti-leukemia-responses-in-mice
#3
Anna Uri, Fred Lühder, Thomas Kerkau, Niklas Beyersdorf
Donor lymphocyte infusions (DLI) together with allogeneic hematopoietic stem cell transplantation (allo-HSCT) are routinely used as second-line treatment for hematological malignancies. Mature T cells in the graft crucially mediate a Graft versus Leukemia (GvL) response, but also attack healthy tissues in the recipient leading to potentially life-threatening acute Graft versus Host Disease (aGvHD). Using inducible CD28 knock-out C57BL/6 mice as T cell donors we have now assessed whether CD28 costimulation of donor CD4+ and/ or CD8+ T cells is required for an efficient GvL effect after allogeneic T cell transplantation into BALB/c recipients...
October 15, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/30319642/endogenous-galectin-1-in-t-lymphocytes-regulates-anti-prostate-cancer-immunity
#4
Enrique Corapi, Gustavo Carrizo, Daniel Compagno, Diego Laderach
The identification of effective new therapies for prostate cancer (PCa) requires a better understanding of the multiple molecular interactions between tumor cells and their associated microenvironment. In this context, galectin-1 (Gal-1) is a key molecule in the determination of the prostatic carcinoma microenviroment; therefore, it is essential to understand all the molecular processes in which this protein is involved. Most of the previous studies found in the literature have focused on the microenvironment remodeling properties of tumor-secreted Gal-1, through its interactions with the glyco-receptors at the cell membrane and the extracellular matrix...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30319363/purinergic-profiling-of-regulatory-t-cells-in-patients-with-episodic-migraine
#5
Dilyara Nurkhametova, Igor Kudryavtsev, Olga Khayrutdinova, Maria Serebryakova, Rashid Altunbaev, Tarja Malm, Rashid Giniatullin
Objectives: Immune responses in migraine are poorly characterized, yet implicated in the disease pathogenesis. This study was carried out to characterize purinergic profiles of T-cells in patients with episodic migraine without aura (MWoA) to provide mechanistic evidence for ATP and adenosine involvement in modulation of immune regulation in migraine. Methods: Peripheral blood samples were obtained from patients with migraine ( n = 16) and age-matched control subjects ( n = 21). Subsets of T-cells were identified by flow cytometry based on specific membrane markers...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/30317947/randomized-clinical-trial-for-the-evaluation-of-immune-modulation-by-yogurt-enriched-with-%C3%AE-glucans-from-lingzhi-or-reishi-medicinal-mushroom-ganoderma-lucidum-agaricomycetes-in-children-from-medellin-colombia
#6
Sandra Lorena Duque Henao, Sergio A Urrego, Andrea M Cano, Edwin A Higuita
Pattern recognition receptor (PRR) agonists are promising for use in modulating immune responses in clinical settings characterized by immune immaturity or deficiency. β-Glucans derived from Ganoderma lucidum have demonstrated immune-modulatory activity both in vitro and in vivo. To evaluate the immunomodulatory activity of orally administered β-glucans, a randomized, double-blinded, placebo-controlled clinical study was performed in asymptomatic children, aged 3 to 5 years old, from Medellin, Colombia. Primary outcomes were the circulating CD8+ T lymphocyte and natural killer cell counts; secondary outcomes were circulating lymphocyte counts (total, CD3+, and CD4+ T cells), serum concentrations of total immunoglobulin A and cytokines, and various hematological parameters...
2018: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/30315942/manufacture-of-car-t-cells-from-mobilized-cyropreserved-peripheral-blood-stem-cell-units-depends-on-monocyte-depletion
#7
Annette Künkele, Christopher Brown, Adam Beebe, Stephanie Mgebroff, Adam J Johnson, Agne Taraseviciute, Lisa S Rolczynski, Cindy A Chang, Olivia C Finney, Julie R Park, Michael C Jensen
Cytotoxic chemotherapy and radiation can render lymphocyte repertoires qualitatively and quantitatively defective. Thus, heavily treated patients are often poor candidates for the manufacture of autologous CAR-T cell products. In the USA and Europe, children with high-risk neuroblastoma undergo apheresis early in the course of their treatment to collect peripheral blood stem cells (PBSCs) for cryopreservation in preparation for high-dose chemotherapy followed by autologous stem cell rescue. Here, we investigate whether these cryopreserved chemotherapy and G-CSF-mobilized PBSCs can be utilized as starting material for CAR-T cell manufacturing...
October 10, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/30315769/crispr-cas9-mediated-hpv-and-pd1-inhibition-produces-a-synergistic-anti-tumor-effect-on-cervical-cancer
#8
Shuai Zhen, Jiaojiao Lu, Ling Hua, Yun-Hui Liu, Wei Chen, Xu Li
Targeted therapy results in objective responses in cervical cancer. However, the responses are short. In contrast, treatment with immune checkpoint inhibitors results in a lower responses rate, but the responses tend to be more durable. Based on these findings, we hypothesized that HPV16 E6/E7-targeted therapy may synergize with the PD-1 pathway blockade to enhance antitumor activity. To test the hypothesis, we described the effects of CRISPR/Cas9 which targeted to the HPV and PD1 in vitro and in vivo. Our data showed that gRNA/cas9 targeted HPV16 E6/E7 induced cervical cancer cell SiHa apoptosis, and suggested that overexpression of PD-L1, induced by HPV16 E6/E7, may be responsible for lymphocyte dysfunction...
October 10, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/30315476/low-t-cell-subsets-prior-to-development-of-virus-associated-cancer-in-hiv-seronegative-men-who-have-sex-with-men
#9
Anupriya Dutta, Hajime Uno, David R Lorenz, Steven M Wolinsky, Dana Gabuzda
Immunological parameters that influence susceptibility to virus-associated cancers in HIV-seronegative individuals are unclear. We conducted a case-control cohort study of immunological parameters associated with development of incident virus-associated cancers among 532 HIV-seronegative men who have sex with men (MSM) enrolled in the Multicenter AIDS Cohort Study (MACS) with median (IQR) 21 (8-26) years of follow-up. Thirty-two incident virus-associated cancers (anal cancer, non-Hodgkin lymphoma, liver cancer, other cancers with etiologies linked to human papillomavirus, Epstein-Barr virus, hepatitis B virus, or human herpesvirus-8) were identified among 3,408 HIV-seronegative men in the MACS during 1984-2010...
October 12, 2018: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/30314757/cd8-t-cell-priming-in-established-chronic-viral-infection-preferentially-directs-differentiation-of-memory-like-cells-for-sustained-immunity
#10
Laura M Snell, Bethany L MacLeod, Jaclyn C Law, Ivan Osokine, Heidi J Elsaesser, Kebria Hezaveh, Russell J Dickson, Marc A Gavin, Cynthia J Guidos, Tracy L McGaha, David G Brooks
CD8+ T cell exhaustion impedes control of chronic viral infection; yet how new T cell responses are mounted during chronic infection is unclear. Unlike T cells primed at the onset of infection that rapidly differentiate into effectors and exhaust, we demonstrate that virus-specific CD8+ T cells primed after establishment of chronic LCMV infection preferentially generate memory-like transcription factor TCF1+ cells that were transcriptionally and proteomically distinct, less exhausted, and more responsive to immunotherapy...
October 1, 2018: Immunity
https://www.readbyqxmd.com/read/30314524/targeting-vegfr2-with-ramucirumab-strongly-impacts-effector-activated-regulatory-t-cells-and-cd8-t-cells-in-the-tumor-microenvironment
#11
Yasuko Tada, Yosuke Togashi, Daisuke Kotani, Takeshi Kuwata, Eichi Sato, Akihito Kawazoe, Toshihiko Doi, Hisashi Wada, Hiroyoshi Nishikawa, Kohei Shitara
BACKGROUND: Several studies have established a correlation between the VEGF-VEGFR2 axis and an immunosuppressive microenvironment; this immunosuppression can be overcome by anti-angiogenic reagents, such as ramucirumab (RAM). However, little is known about the immunological impact of anti-angiogenic reagents within the tumor microenvironment in human clinical samples. This study aimed at investigating the effects of RAM on the tumor microenvironmental immune status in human cancers. METHODS: We prospectively enrolled 20 patients with advanced gastric cancer (GC) who received RAM-containing chemotherapy...
October 11, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30312276/analyses-of-mitochondrial-dna-and-immune-phenotyping-suggest-accelerated-t-cell-turnover-in-treated-hiv
#12
Marta Massanella, Maile Y Karris, Josué Pérez-Santiago, Christina Yek, Andrej Vitomirov, Sanjay R Mehta
BACKGROUND: HIV infection is associated with premature aging, and mitochondrial integrity is compromised during the aging process. Because mitochondrial toxicity is a consequence of antiretroviral therapies (ARTs), we hypothesized HIV and long-term ART would correlate with immunosenescence and mitochondrial DNA (mtDNA) pathology. SETTING: Thirteen older HIV-infected individuals (aged >40 years) with virologic suppression (stratified by duration of ART) were compared with 10 uninfected controls well-matched for age...
November 1, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/30311623/immunovirological-outcome-and-hiv-1-dna-decay-in-a-small-cohort-of-hiv-1-infected-patients-deintensificated-from-abacavir-lamivudine-dolutegravir-to-lamivudine-plus-dolutegravir
#13
Massimiliano Lanzafame, Stefano Nicole, Sebastiano Rizzardo, Daniela Piacentini, Sheila Chiesi, Emanuela Lattuada, Erica Diani, Maria Carelli, Sandro Vento, Davide Gibellini
Combination abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) is approved as a first-line treatment for antiretroviral naïve patients. This report investigated the immunovirological outcome and total HIV-1 DNA decay in a small cohort of naïve HIV-1-positive patients treated with this regimen. In the presence of viral suppression and increased lymphocyte T CD4+ cells, the quantitative analysis of total HIV-1 DNA content revealed a significant decay after 12 months of treatment. Subsequently, we deintensificated the treatment of these patients from (ABC/3TC/DTG) to lamivudine plus dolutegravir (3TC/DTG) after 12 months of virological suppression, as a strategy of "induction-maintenance" therapy...
October 12, 2018: New Microbiologica
https://www.readbyqxmd.com/read/30309848/selective-loss-of-function-variants-in-il6st-cause-hyper-ige-syndrome-with-distinct-impairments-of-t-cell-phenotype-and-function
#14
Tala Shahin, Dominik Aschenbrenner, Deniz Cagdas, Sevgi Köstel Bal, Cecilia Domínguez Conde, Wojciech Garncarz, David Medgyesi, Tobias Schwerd, Betül Karaatmaca, Pınar Gur Cetinkaya, Saliha Esenboga, Stephen R F Twigg, Andrew Cant, Andrew O M Wilkie, Ilhan Tezcan, Holm H Uhlig, Kaan Boztug
Hyper-IgE Syndromes comprise a group of inborn errors of immunity. STAT3-deficient hyper-IgE syndrome is characterized by elevated serum IgE levels, recurrent infections and eczema, and characteristic skeletal anomalies. A loss-of-function biallelic mutation in IL6ST encoding the GP130 receptor subunit (p.N404Y) has very recently been identified in a singleton patient (herein referred to as PN404Y) as a novel etiology of hyper-IgE syndrome. Here, we studied a patient with hyper-IgE syndrome caused by a novel homozygous mutation in IL6ST (p...
October 11, 2018: Haematologica
https://www.readbyqxmd.com/read/30308300/targeted-codelivery-of-doxorubicin-and-il-36%C3%AE-expression-plasmid-for-an-optimal-chemo-gene-combination-therapy-against-cancer-lung-metastasis
#15
Yichao Chen, Jingjing Sun, Yixian Huang, Yanhua Liu, Lei Liang, Da Yang, Binfeng Lu, Song Li
Cancer metastasis is the main cause for the high mortality in breast cancer patients. In this work we developed a polymer POEG-st-Pmor for targeted co-delivery of IL-36γ expression plasmid and doxorubicin (Dox) to lung metastasis of breast cancer. The polymer readily formed micelles that were effective in loading Dox and simultaneously forming complexes with IL-36γ plasmid. Interestingly, particles co-loaded with Dox and plasmid was significantly smaller and more stable than the particles loaded with Dox only...
October 8, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/30308209/the-role-of-%C3%AE-%C3%AE-t-cells-in-spontaneous-regression-of-melanoma-tumors-in-swine
#16
Jana Cizkova, Zuzana Sinkorova, Kristyna Strnadova, Monika Cervinkova, Vratislav Horak, Jiri Sinkora, Katerina Stepanova, Marek Sinkora
Using a porcine model, we describe Melanoma-Associated CD4+ CD8hi T-lymphocytes (MATL) in peripheral blood that increase during melanoma regression. These MATL possess the CD4+ CD8hi phenotype and they have their direct counterparts in Tumor Infiltrating Lymphocytes (TIL) isolated from melanoma loci. Both MATL and CD4+ CD8hi TIL have a similar expression of selected markers indicating that they represent effector/memory αβ T-cell subset. Moreover, although TIL also contain CD4- CD8+ T-cells, only CD4+ CD8hi TIL expand during melanoma regression...
October 8, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/30307371/acute-sarcoidosis-in-a-multiple-sclerosis-patient-after-alemtuzumab-treatment
#17
Jonas Graf, Marius Ringelstein, Klaudia Lepka, Jörg Schaller, Helmut Quack, Hans-Peter Hartung, Orhan Aktas, Philipp Albrecht
BACKGROUND: Understanding the long-term effect of alemtuzumab on the immune system of multiple sclerosis (MS) patients is crucial. OBJECTIVE: To report a case of acute sarcoidosis (Löfgren's syndrome) in a relapsing-remitting MS patient, 1.5 years after the second course of alemtuzumab treatment. CASE REPORT: Sarcoidosis was confirmed dermatohistologically, radiologically, and serologically. Analysis of the lymphocyte subpopulations showed a persistent effect of alemtuzumab treatment (CD4/CD8 ratio increased, absolute lymphocyte count of CD19-positive cells increased while CD3/4/8-positive cells were decreased)...
October 11, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/30305631/complement-receptor-cd46-co-stimulates-optimal-human-cd8-t-cell-effector-function-via-fatty-acid-metabolism
#18
Giuseppina Arbore, Erin E West, Jubayer Rahman, Gaelle Le Friec, Nathalie Niyonzima, Mehdi Pirooznia, Ilker Tunc, Polychronis Pavlidis, Nicholas Powell, Yuesheng Li, Poching Liu, Aude Servais, Lionel Couzi, Veronique Fremeaux-Bacchi, Leo Placais, Alastair Ferraro, Patrick R Walsh, David Kavanagh, Behdad Afzali, Paul Lavender, Helen J Lachmann, Claudia Kemper
The induction of human CD4+ Th1 cells requires autocrine stimulation of the complement receptor CD46 in direct crosstalk with a CD4+ T cell-intrinsic NLRP3 inflammasome. However, it is unclear whether human cytotoxic CD8+ T cell (CTL) responses also rely on an intrinsic complement-inflammasome axis. Here we show, using CTLs from patients with CD46 deficiency or with constitutively-active NLRP3, that CD46 delivers co-stimulatory signals for optimal CTL activity by augmenting nutrient-influx and fatty acid synthesis...
October 10, 2018: Nature Communications
https://www.readbyqxmd.com/read/30305604/diosgenin-promotes-antitumor-immunity-and-pd-1-antibody-efficacy-against-melanoma-by-regulating-intestinal-microbiota
#19
Mengxue Dong, Zhefeng Meng, Kudelaidi Kuerban, Feilong Qi, Jiayang Liu, Yuxi Wei, Qian Wang, Shanshan Jiang, Meiqing Feng, Li Ye
Diosgenin, a natural steroidal saponin, can exert antitumor effect by regulating immune function and improving intestinal microbiota. The response to anti-PD-1 immunotherapy is associated with intestinal microbiota and effector T cells in tumor microenvironment. We hypothesize that the modulation of diosgenin on intestinal microbiota can facilitate antitumor immunity and the therapeutic efficacy of PD-1 antibody. In melanoma-bearing C57BL/6 mice, we observed that the anti-melanoma effect of diosgenin relied more on antitumor immunity than direct tumor inhibition activity evidenced by obvious CD4+ /CD8+ T-cell infiltration and IFN-γ expression in tumor tissues, and it could improve the compositions of intestinal microbiota...
October 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/30305342/a-four-gene-decision-tree-signature-classification-of-triple-negative-breast-cancer-implications-for-targeted-therapeutics
#20
Jelmar Quist, Hasan Mirza, Maggie C U Cheang, Melinda L Telli, Joyce O'Shaughnessy, Christopher J Lord, Andrew N J Tutt, Anita Grigoriadis
The molecular complexity of triple-negative breast cancers (TNBCs) provides a challenge for patient management. We set out to characterise this heterogeneous disease by combining transcriptomics and genomics data, with the aim of revealing convergent pathway dependencies with the potential for treatment intervention. A Bayesian algorithm was used to integrate molecular profiles in two TNBC cohorts, followed by validation using five independent cohorts (n = 1,168), including three clinical trials. A four-gene decision tree signature was identified which robustly classified TNBCs into six subtypes...
October 10, 2018: Molecular Cancer Therapeutics
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