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https://www.readbyqxmd.com/read/29339209/extratumoral-pd-1-blockade-does-not-perpetuate-obesity-associated-inflammation-in-esophageal-adenocarcinoma
#1
Karen C Galvin, Melissa J Conroy, Suzanne L Doyle, Margaret R Dunne, Ronan Fahey, Emma Foley, Katie E O'Sullivan, Derek G Doherty, Justin G Geoghegan, Narayanasamy Ravi, Cliona O'Farrelly, John V Reynolds, Joanne Lysaght
Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming cancer treatment for inoperable or advanced disease. As the incidence of obesity-associated malignancies, including esophageal adenocarcinoma (EAC) continue to increase and treatment with checkpoint inhibitors are being FDA approved for a broader range of cancers, it is important to assess how anti-PD-1 treatment might exacerbate pre-existing inflammatory processes at other sites. Outside the EAC tumor, the omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells...
January 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29312617/t-cell-responses-to-kshv-infection-a-systematic-approach
#2
Romin Roshan, Nazzarena Labo, Matthew Trivett, Wendell Miley, Vickie Marshall, Lori Coren, Elena M Cornejo Castro, Hannah Perez, Benjamin Holdridge, Eliza Davis, Rodrigo Matus-Nicodemos, Victor I Ayala, Raymond Sowder, Kathleen M Wyvill, Karen Aleman, Christine Fennessey, Jeffrey Lifson, Mark N Polizzotto, Daniel Douek, Brandon Keele, Thomas S Uldrick, Robert Yarchoan, Claes Ohlen, David Ott, Denise Whitby
Prior studies of T-cell responses to KSHV have included relatively few participants and focused on relatively few KSHV antigens. To provide a more comprehensive analysis, we investigated T-cell responses to the whole KSHV proteome using IFN-γ ELISpot. Using ∼7,500 overlapping 15mer peptides we generated one to three peptide pools for each of the 82 KSHV ORFs. IFN-γ ELISpot analysis of PBMCs from 19 patients with a history of KSHV-associated disease and 24 healthy donors (11 KSHV seropositive) detected widely varied responses...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29301753/exosomes-associated-with-human-ovarian-tumors-harbor-a-reversible-checkpoint-of-t-cell-responses
#3
Gautam N Shenoy, Jenni L Loyall, Orla Maguire, Vandana Iyer, Raymond J Kelleher, Hans Minderman, Paul K Wallace, Kunle Odunsi, Sathy V Balu-Iyer, Richard B Bankert
Nano-sized membrane-encapsulated extracellular vesicles isolated from the ascites fluids of ovarian cancer patients are identified as exosomes based on their biophysical and compositional characteristics. We report here that T cells pulsed with these tumor-associated exosomes during TCR-dependent activation inhibit various activation endpoints including translocation of NFkB and NFAT into the nucleus, upregulation of CD69 and CD107a, production of cytokines and cell proliferation. Additionally, the activation of virus-specific CD8+ T cells that are stimulated with the cognate viral peptides presented in the context of class I MHC is also suppressed by the exosomes...
January 4, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29236750/identification-of-gad65-aa-114-122-reactive-memory-like-nk-cells-in-newly-diagnosed-type-1-diabetic-patients-by-hla-class-i-pentamers
#4
Valentina Perri, Elena Gianchecchi, Loredana Cifaldi, Marsha Pellegrino, Ezio Giorda, Marco Andreani, Marco Cappa, Alessandra Fierabracci
Type 1 diabetes is an autoimmune disease, in which pancreatic β cells are destroyed by autoreactive T cells in genetically predisposed individuals. Serum beta cell autoantibody specificities have represented the mainstay for classifying diabetes as autoimmune-mediated and for stratifying risk in first-degree relatives. In recent years, approaches were attempted to solve the difficult issue of detecting rare antigen-specific autoreactive T cells and their significance to etiopathogenesis such as the use of the MHC multimer technology...
2017: PloS One
https://www.readbyqxmd.com/read/29235226/reduced-therapeutic-effect-of-antiviral-drugs-in-patients-with-hepatitis-b-virus-reactivation-after-hematopoietic-stem-cell-transplantation
#5
Masamichi Kimura, Koji Nishikawa, Hisashi Sakamaki, Masashi Mizokami, Kiminori Kimura
BACKGROUND: Patients with resolved Hepatitis B virus (HBV) infection following hematopoietic stem cell transplantation (HSCT) are potentially at high risk of HBV reactivation. Although anti-viral drug therapy is recommended when HBV DNA reappears in the serum, drug efficacy after HBV reactivation remains unclear. METHODS: Host immune response against HBV was investigated via immunological analyses at 12 months after entecavir (ETV) treatment in six HSCT-treated and five non-HSCT-treated patients with HBV reactivation, and 18 patients with chronic hepatitis B (CHB)...
December 13, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29218366/haploidentical-natural-killer-cells-induce-remissions-in-non-hodgkin-lymphoma-patients-with-low-levels-of-immune-suppressor-cells
#6
Veronika Bachanova, Dhifaf Sarhan, Todd E DeFor, Sarah Cooley, Angela Panoskaltsis-Mortari, Bruce R Blazar, Julie M Curtsinger, Linda Burns, Daniel J Weisdorf, Jeffrey S Miller
We report a novel phase 2 clinical trial in patients with poor prognosis refractory non-Hodgkin lymphoma (NHL) testing the efficacy of haploidentical donor natural killer (NK) cell therapy (NK dose 0.5-3.27 × 107 NK cells/kg) with rituximab and IL-2 (clinicaltrials.gov NCT01181258). Therapy was tolerated without graft-versus-host disease, cytokine release syndrome, or neurotoxicity. Of 14 evaluable patients, 4 had objective responses (29%; 95% CI 12-55%) at 2 months: 2 had complete response lasting 3 and 9 months...
December 7, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29213079/human-cd26high-t-cells-elicit-tumor-immunity-against-multiple-malignancies-via-enhanced-migration-and-persistence
#7
Stefanie R Bailey, Michelle H Nelson, Kinga Majchrzak, Jacob S Bowers, Megan M Wyatt, Aubrey S Smith, Lillian R Neal, Keisuke Shirai, Carmine Carpenito, Carl H June, Michael J Zilliox, Chrystal M Paulos
CD8+ T lymphocytes mediate potent immune responses against tumor, but the role of human CD4+ T cell subsets in cancer immunotherapy remains ill-defined. Herein, we exhibit that CD26 identifies three T helper subsets with distinct immunological properties in both healthy individuals and cancer patients. Although CD26neg T cells possess a regulatory phenotype, CD26int T cells are mainly naive and CD26high T cells appear terminally differentiated and exhausted. Paradoxically, CD26high T cells persist in and regress multiple solid tumors following adoptive cell transfer...
December 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29188237/fewer-circulating-natural-killer-cells-28-days-after-double-cord-blood-transplantation-predicts-inferior-survival-and-il-15-response
#8
Rachel J Bergerson, Robin Williams, Hongbo Wang, Ryan Shanley, Gretchen Colbenson, Alyssa Kerber, Sarah Cooley, Julie Curtsinger, Martin Felices, Jeffrey S Miller, Michael R Verneris
Natural Killer (NK) cell immune reconstitution after double umbilical cord blood transplantation (dUCBT) is rapid and thought to be involved in graft vs. leukemia (GvL) reactions. To investigate the role of NK cell recovery on clinical outcomes, the absolute number of NK cells at Day 28 after dUCBT was determined and patients with low numbers of NK cells had inferior two year disease-free survival (hazard ratio 1.96; p=0.04). A detailed developmental and functional analysis of the recovering NK cells was performed to link NK recovery and patient survival...
December 27, 2016: Blood Advances
https://www.readbyqxmd.com/read/29182664/differential-inhibitory-and-activating-nk-cell-receptor-levels-and-nk-nkt-like-cell-functionality-in-chronic-and-recovered-stages-of-chikungunya
#9
Subrat Thanapati, Mohini A Ganu, Anuradha S Tripathy
The role of natural killer (NK; CD3-CD56+)/NKT (CD3+CD56+)-like cells in chikungunya virus (CHIKV) disease progression/recovery remains unclear. Here, we investigated the expression profiles and function of NK and NKT-like cells from 35 chronic chikungunya patients, 30 recovered individuals, and 69 controls. Percentage of NKT-like cells was low in chronic chikungunya patients. NKp30+, CD244+, DNAM-1+, and NKG2D+ NK cell percentages were also lower (MFI and/or percentage), while those of CD94+ and NKG2A+ NKT-like cells were higher (MFI and/or percentage) in chronic patients than in recovered subjects...
2017: PloS One
https://www.readbyqxmd.com/read/29179214/cetuximab-enhanced-the-cytotoxic-activity-of-immune-cells-during-treatment-of-colorectal-cancer
#10
Lin Wang, Yingfeng Wei, Weijia Fang, Chong Lu, Jianing Chen, Guangying Cui, Hongyan Diao
BACKGROUND/AIMS: Cetuximab is a chimeric IgG1 monoclonal antibody which targets the extracellular domain of epidermal growth factor receptor. This antibody is widely used for colorectal cancer (CRC) treatment but its influence on the immune system is incompletely understood. METHODS: The immune influence of cetuximab therapy in CRC patients was investigated by analyzing peripheral blood mononuclear cells using flow cytometry. We undertook in vitro cytotoxicity and cytokine-profile assays to ascertain the immunomodulatory effect of cetuximab treatment...
November 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29113351/b7-h4-overexpression-is-essential-for-early-hepatocellular-carcinoma-progression-and-recurrence
#11
Fu-Biao Kang, Ling Wang, Dian-Xing Sun, Hai-Jun Li, Dong Li, Yan Wang, Ji-Wen Kang
B7-H4, another member of costimulatory molecule, has been shown to be overexpressed in multiple types of tumors, including hepatocellular carcinoma (HCC). However, the specific biological role of B7-H4 in HCC still needs to be further explored. In this study, we observed that B7-H4 was highly overexpressed in HCC tissues and cells, and its overexpression strongly correlated with patient's TNM stage, overall survival and early recurrence. Downregulation of B7-H4 significantly suppressed cell growth, invasion, and stemness of HCC by inducing apoptosis in the in vitro experiment...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093082/according-to-hcv-infection-stage-il-7-plus-4-1bb-triggering-alone-or-combined-with-pd-1-blockade-increases-traf1-low-hcv-specific-cd8-cell-reactivity
#12
Elia Moreno-Cubero, Dolores Subirá, Eduardo Sanz-de-Villalobos, Trinidad Parra-Cid, Antonio Madejón, Joaquín Miquel, Antonio Olveira, Alejandro González-Praetorius, Javier García-Samaniego, Juan-Ramón Larrubia
Hepatitis C virus (HCV)-specific CD8(+) T cells suffer a progressive exhaustion during persistent HCV infection (PI). This process could involve the positive immune checkpoint 4-1BB/4-1BBL, through the loss of its signal transducer TRAF1. To address this issue, peripheral HCV-specific CD8(+) T cells (Pentamer(+)/CD8(+)) from patients with PI and resolved infection after treatment (RI) were studied. Duration of HCV infection and liver fibrosis progression rate inversely correlated with the likelihood of detecting peripheral pentamer(+)/CD8(+) cells...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29089645/identification-and-characterization-of-hla-a24-specific-xbp1-cd138-syndecan-1-and-cs1-slamf7-peptides-inducing-antigens-specific-memory-cytotoxic-t-lymphocytes-targeting-multiple-myeloma
#13
J Bae, T Hideshima, G L Zhang, J Zhou, D B Keskin, N C Munshi, K C Anderson
XBP1 (X-box binding protein 1), CD138 (Syndecan-1), and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29055015/small-molecule%C3%A2-inhibition-of-pd-1-transcription-is-an-effective-alternative-to-antibody-blockade-in-cancer-therapy
#14
Alison Taylor, David Rothstein, Christopher E Rudd
The impact of PD-1 immune checkpoint therapy prompts exploration of other strategies to downregulate PD-1 for cancer therapy. We previously showed that the serine/threonine kinase, glycogen synthase kinase GSK-3α/β, is a central regulator of PD-1 transcription in CD8+ T cells. Here, we show that the use of small molecule inhibitors of GSK-3α/β (GSK-3i) to reduce pcdc1 (PD-1) transcription and expression was as effective as anti-PD-1 and PDL-1 blocking antibodies in the control of B16 melanoma, or EL4 lymphoma, in primary tumor and metastatic settings...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29040297/decreased-nk-cell-immunity-in-kidney-transplant-recipients-late-post-transplant-and-increased-nk-cell-immunity-in-patients-with-recurrent-miscarriage
#15
Li Zhu, Mostafa Aly, Haihao Wang, Hristos Karakizlis, Rolf Weimer, Christian Morath, Ruben Jeremias Kuon, Bettina Toth, Gerhard Opelz, Volker Daniel
BACKGROUND: There is evidence that NK-cell reactivity might affect graft outcome in transplant recipients and pregnancy in women. METHOD: NK-cell subsets were determined in whole blood using eight-colour-fluorescence flow cytometry in patients before and after renal transplantation, patients with recurrent miscarriage (RM) and healthy controls (HC). RESULTS: Patients late post-transplant (late-Tx) with functioning renal transplants showed abnormally low CD56dimCD16+ NK-cells containing both perforin and granzyme (vs HC p = 0...
2017: PloS One
https://www.readbyqxmd.com/read/29038620/dengue-virus-induces-nk-cell-activation-through-trail-expression-during-infection
#16
Mariana Gandini, Fabienne Petitinga-Paiva, Cíntia Ferreira Marinho, Gladys Correa, Luzia Maria De Oliveira-Pinto, Luiz José de Souza, Rivaldo Venâncio Cunha, Claire Fernandes Kubelka, Elzinandes Leal de Azeredo
Dengue is an acute febrile illness with a wide spectrum of signs and symptoms ranging from mild to severe forms characterized by plasma leakage that can be fatal. NK cells are one of the main effectors in early infection and may play an important role in dengue pathogenesis. We investigated NK cell involvement during dengue infection. A higher frequency of NK cell subsets and TRAIL+NK cells was found in mild DF cases when compared to that in severe cases or healthy donors. NK activation markers such as CD107a and TLR3 were upregulated in patients' cells compared to those in healthy donors...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29023759/cord-blood-derived-t-cells-allow-the-generation-of-a-more-na%C3%A3-ve-tumor-reactive-cytotoxic-t-cell-phenotype
#17
Julian Kwoczek, Sebastian B Riese, Sabine Tischer, Szilvia Bak, Julia Lahrberg, Mathias Oelke, Holger Maul, Rainer Blasczyk, Martin Sauer, Britta Eiz-Vesper
BACKGROUND: Transplantation of hematopoietic stem cells (HSCs) from peripheral blood (PB) or cord blood (CB) is well established. HSCs from CB are associated with a lower risk of graft-versus-host disease (GVHD), but antigen-independent expanded CB- and PB-derived T cells can induce GVHD in allo-HSC recipients. CB-derived cells might be more suitable for adoptive immunotherapy as they have unique T-cell characteristics. Here, we describe functional differences between CB and PB T cells stimulated with different cytokine combinations involved in central T-cell activation...
October 11, 2017: Transfusion
https://www.readbyqxmd.com/read/29022005/systemic-and-terminal-ileum-mucosal-immunity-elicited-by-oral-immunization-with-the-ty21a-typhoid-vaccine-in-humans
#18
Jayaum S Booth, Seema A Patil, Leyla Ghazi, Robin Barnes, Claire M Fraser, Alessio Fasano, Bruce D Greenwald, Marcelo B Sztein
BACKGROUND & AIMS: Systemic cellular immunity elicited by the Ty21a oral typhoid vaccine has been extensively characterized. However, very limited data are available in humans regarding mucosal immunity at the site of infection (terminal ileum [TI]). Here we investigated the host immunity elicited by Ty21a immunization on terminal ileum-lamina propria mononuclear cells (LPMC) and peripheral blood in volunteers undergoing routine colonoscopy. METHODS: We characterized LPMC-T memory (TM) subsets and assessed Salmonella enterica serovar Typhi (S Typhi)-specific responses by multichromatic flow cytometry...
November 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28960213/impaired-polyfunctionality-of-cd8-t-cells-in-severe-sepsis-patients-with-human-cytomegalovirus-reactivation
#19
Young Joon Choi, Sun Bean Kim, Jong Hoon Kim, Su-Hyung Park, Moo Suk Park, June Myung Kim, Sang Hoon Han, Eui-Cheol Shin
Human cytomegalovirus (HCMV) establishes a lifelong chronic latent infection and often reactivates in immunocompromised patients. In addition, HCMV reactivates in patients with sepsis or other critical illnesses, particularly in patients with poor prognoses. However, the immunological characteristics of sepsis patients with HCMV reactivation have not been elucidated. In the present study, we examined T-cell responses in severe sepsis patients with and without HCMV reactivation. First, HCMV pp65-specific T-cell functions were assessed by intracellular cytokine staining (ICS) for IFN-γ, TNF-α, and MIP-1β and by CD107a staining...
September 29, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28938026/hiv-exposed-seronegative-hesn-compared-to-hiv-infected-individuals-have-higher-frequencies-of-telomeric-killer-immunoglobulin-like-receptor-kir-b-motifs-contribution-of-kir-b-motif-encoded-genes-to-nk-cell-responsiveness
#20
Elise Jackson, Cindy Xinyu Zhang, Zahra Kiani, Irene Lisovsky, Benjamin Tallon, Alexa Del Corpo, Louise Gilbert, Julie Bruneau, Réjean Thomas, Pierre Côté, Benoit Trottier, Roger LeBlanc, Danielle Rouleau, Cécile Tremblay, Christos M Tsoukas, Jean-Pierre Routy, Xiaoyan Ni, Tsoarello Mabanga, Nicole F Bernard
Previously, we showed that Killer Immunoglobulin-like Receptor (KIR)3DS1 homozygotes (hmz) are more frequent in HIV exposed seronegative (HESN) than in recently HIV infected (HIV+) individuals. KIR3DS1 encodes an activating Natural Killer (NK) cell receptor (NKR). The link between KIR genotype and HIV outcomes likely arises from the function that NK cells acquire through expression of particular NKRs. An initial screen of 97 HESN and 123 HIV+ subjects for the frequency of KIR region gene carriage observed between-group differences for several telomeric KIR region loci...
2017: PloS One
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