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https://www.readbyqxmd.com/read/29113351/b7-h4-overexpression-is-essential-for-early-hepatocellular-carcinoma-progression-and-recurrence
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#11
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28894091/expansion-of-cytotoxic-natural-killer-cells-using-irradiated-autologous-peripheral-blood-mononuclear-cells-and-anti-cd16-antibody
#12
Hong-Rae Lee, Cheol-Hun Son, Eun-Kyoung Koh, Jae-Ho Bae, Chi-Dug Kang, Kwangmo Yang, You-Soo Park
Natural killer (NK) cells are considered a promising strategy for cancer treatment. Various methods for large-scale NK cell expansion have been developed, but they should guarantee that no viable cells are mixed with the expanded NK cells because most methods involve cancer cells or genetically modified cells as feeder cells. We used an anti-CD16 monoclonal antibody (mAb) and irradiated autologous peripheral blood mononuclear cells (PBMCs) (IrAPs) to provide a suitable environment (activating receptor-ligand interactions) for the NK cell expansion...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28887642/evaluation-of-the-functional-capacity-of-nk-cells-of-melanoma-patients-in-an-in-vitro-model-of-nk-cell-contact-with-k562-and-femx-tumor-cell-lines
#13
Gordana Konjevic, Ana Vuletic, Katarina Mirjacic Martinovic, Ana Krivokuca, Radmila Jankovic, Nada Babovic
NK cells of metastatic melanoma (MM) patients display impaired function, making them incapable to mount an effective antitumor response. In this study, we evaluated immunophenotypic characteristics and functional capacity of CD3(-)CD16(+) NK cells of MM patients in an in vitro model based on NK cell contact with an NK sensitive, K562, and a tumor-specific, melanoma FemX tumor cell line. Although our results indicate similar NK cell antitumor cytotoxic potential of MM patients in contact with both cell lines based on the expression of CD107a degranulation marker, there is a discrepancy in NK cell IFNγ production, as it is not significantly induced by FemX tumor cells, found to be, contrary to K562, HLA class I positive...
September 8, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28883824/natural-killer-nk-cell-education-differentially-influences-hiv-antibody-dependent-nk-cell-activation-and-antibody-dependent-cellular-cytotoxicity
#14
REVIEW
Nicole F Bernard, Zahra Kiani, Alexandra Tremblay-McLean, Sanket A Kant, Christopher E Leeks, Franck P Dupuy
Immunotherapy using broadly neutralizing antibodies (bNAbs) endowed with Fc-mediated effector functions has been shown to be critical for protecting or controlling viral replication in animal models. In human, the RV144 Thai trial was the first trial to demonstrate a significant protection against HIV infection following vaccination. Analysis of the correlates of immune protection in this trial identified an association between the presence of antibody-dependent cellular cytotoxicity (ADCC) mediated by immunoglobulin G (IgG) antibodies (Abs) to HIV envelope (Env) V1/V2 loop structures and protection from infection, provided IgA Abs with competing specificity were not present...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28870466/il-12-and-il-7-synergize-to-control-mucosal-associated-invariant-t-cell-cytotoxic-responses-to-bacterial-infection
#15
Joshua C Wallington, Anthony P Williams, Karl J Staples, Tom M A Wilkinson
BACKGROUND: Bacterial respiratory tract infections and exacerbations of chronic lung diseases are commonly caused by nontypeable Haemophilus influenzae (NTHi). Cell-mediated cytotoxicity might be key to controlling infection, but the responses of NTHi-specific T-cell populations are not well understood. Mucosal-associated invariant T (MAIT) cells are a recently discovered, innate-like subset of T cells with cytotoxic function, the role of which in lung immunity is unclear. OBJECTIVE: The aim of this study was to determine the mechanisms behind conventional T-cell and MAIT cell cytotoxic responses to NTHi...
September 1, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28866803/personalized-ex-vivo-multiple-peptide%C3%A2-enrichment-and-detection-of-t-cells-reactive-to-multiple-tumor-associated-antigens-in-prostate-cancer-patients
#16
Pavla Taborska, Dmitry Stakheev, Zuzana Strizova, Katerina Vavrova, Michal Podrazil, Jirina Bartunkova, Daniel Smrz
Personalized peptide vaccination is a promising immunotherapeutic approach in prostate cancer (PCa). We therefore examined whether an approach, utilizing personalized multiple peptide-mediated ex vivo enrichment with effector T cells reactive to multiple tumor-associated antigens (TAAs), could be employed as a basis for the development of T cell immunotherapy of PCa. In this study, we used the non-adherent fraction (lymphocytes) of cryopreserved peripheral blood mononuclear cells from a leukapheretic product of biochemically recurrent (BR, n = 14) and metastatic hormone-refractory (HR, n = 12) PCa patients...
September 2, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28858434/cd4-cd28-null-t-cells-are-not-alloreactive-unless-stimulated-by-interleukin-15
#17
B Dedeoglu, N H R Litjens, M Klepper, R Kraaijeveld, W Verschoor, C C Baan, M G H Betjes
Proinflammatory, cytotoxic CD4(+) CD28(null) T cells can be substantially expanded in patients with end-stage renal disease. These cells have been associated with the risk for rejection, but their alloreactive potential is unknown. CD4(+) CD28(null) T cells were stimulated with HLA-mismatched antigen presenting cells in the absence/presence of exogenous cytokines. Alloreactive potential was evaluated based on proliferation, degranulation, cytotoxicity, and cytokine production. Further, their suppressive capacity was assessed by measuring inhibition of proliferating alloreactive CD28(+) T cells...
August 31, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28818311/characterization-of-the-flow-cytometric-assay-for-ex%C3%A2-vivo-monitoring-of-cytotoxicity-mediated-by-antigen-specific-cytotoxic-t-lymphocytes
#18
Akira Takagi, Yutaka Horiuchi, Masanori Matsui
Several non-radioactive methods have widely been utilized to detect antigen-specific cytotoxic T lymphocyte (CTL) responses instead of the classical (51)Cr-release assay. These methods include intracellular cytokine staining, major histocompatibility complex-class I tetramers, and the CD107a mobilization assay. However, they do not directly measure target-cell death. In contrast, several attempts have been made to develop the flow cytometric CTL (FC-CTL) assay for evaluation of cytotoxicity. However, further improvement is necessary for it to become standardized...
October 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28810810/reduced-expression-of-siglec-7-nkg2a-and-cd57-on-terminally-differentiated-cd56-cd16-nk-cell-subset-is-associated-with-nk-cell-dysfunction-in-chronic-hiv-1-clade-c-infection
#19
Michael Zulu, Kewreshini Naidoo, Zenele Mncube, Manjeetha Jaggernath, Philip Jr Goulder, Thumbi Ndung'u, Marcus Altfeld, Christina Fanesa Thobakgale
BACKGROUND: HIV-1 viremia has been shown to induce several phenotypic and functional abnormalities in natural killer (NK) cells. To assess immune defects associated with HIV viremia, we examined NK cell function, differentiation status and phenotypic alterations based on expression of inhibitory and activating receptors on NK cells in HIV-1 subtype C chronically infected participants from Durban, South Africa. METHODS: NK cell phenotypic profiles were characterized by assessing Siglec-7, NKG2A and NKG2C markers on frozen peripheral blood mononuclear cells (PBMCs) from viremic, antiretroviral therapy (ART)-naïve HIV-1 chronically infected participants (n=23), HIV-1 chronically infected participants who have been on combination antiretroviral therapy (cART) for at least 12 months (n=23) compared to healthy donors (n=23)...
August 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28761354/pd-1-blockade-restores-impaired-function-of-ex-vivo-expanded-cd8-t-cells-and-enhances-apoptosis-in-mismatch-repair-deficient-epcam-pd-l1-cancer-cells
#20
Rajeev Kumar, Fang Yu, Yuan-Huan Zhen, Bo Li, Jun Wang, Yuan Yang, Hui-Xin Ge, Ping-Sheng Hu, Jin Xiu
BACKGROUND: Adoptive T cell therapy has been proven to be a promising modality for the treatment of cancer patients in recent years. However, the increased expression of inhibitory receptors could negatively regulate the function and persistence of transferred T cells which mediates T cell anergy, exhaustion, and tumor regression. In this study, we investigated increased cytotoxic activity after the blockade of PD-1 for effective immunotherapy. METHODS: The cytotoxic function of expanded CD8(+) CTLs and interactions with tumor cells investigated after blocking of PD-1...
2017: OncoTargets and Therapy
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