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https://www.readbyqxmd.com/read/29791021/immtac-anti-pd-1-combination-to-enhance-killing-of-cancer-cells-by-reversing-treg-mediated-immunosuppression
#1
Huanling Zhang, Yanyan Li, Xiaoping Liu, Zhaoduan Liang, Mengyong Yan, Qiang Liu, Anan Chen, Yifeng Bao, Chengzhi Zhou, Shiyue Li, Cassian Yee, Yi Li
Recently, bi-functional molecules that can redirect immune effectors to tumor cells have emerged as potentially robust mediators of tumor regression in clinical trials. Two modalities, in particular, bi-specific antibodies for T cell redirection and activation (BiTe) and immune-mobilizing monoclonal T-cell receptors against cancer (ImmTAC) are being evaluated in efficacy studies as 'off-the-shelf' reagents. Optimal therapy will require an understanding and means to address regulatory mechanisms of limiting efficacy...
May 23, 2018: Immunology
https://www.readbyqxmd.com/read/29749611/proteomic-definition-of-human-mucosal-associated-invariant-t-cells-determines-their-unique-molecular-effector-phenotype
#2
Björn Bulitta, Werner Zuschratter, Isabel Bernal, Dunja Bruder, Frank Klawonn, Martin von Bergen, Henrikus Stephanus Paulus Garritsen, Lothar Jänsch
Mucosal-associated invariant T cells (MAIT) constitute the most abundant anti-bacterial CD8+ T cell population in humans. MR1/TCR-activated MAIT cells were reported to organize cytotoxic and innate-like responses but knowledge about their molecular effector phenotype is still fragmentary. Here, we have examined the functional inventory of human MAIT cells (CD3+Vα7.2+CD161+) in comparison with those from conventional non-MAIT CD8+ T cells (cCD8+ ) and NK cells. Quantitative mass spectrometry characterized 5500 proteins of primary MAIT cells and identified 160 and 135 proteins that discriminate them from cCD8+ T cells and NK cells donor-independently...
May 11, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29743316/hla-f-on-hla-null-721-221-cells-activates-primary-nk-cells-expressing-the-activating-killer-ig-like-receptor-kir3ds1
#3
Zahra Kiani, Franck P Dupuy, Julie Bruneau, Bertrand Lebouché, Cindy X Zhang, Elise Jackson, Irene Lisovsky, Sandrina da Fonseca, Daniel E Geraghty, Nicole F Bernard
NK cells elicit important responses against transformed and virally infected cells. Carriage of the gene encoding the activating killer Ig-like receptor KIR3DS1 is associated with slower time to AIDS and protection from HIV infection. Recently, open conformers of the nonclassical MHC class Ib Ag HLA-F were identified as KIR3DS1 ligands. In this study, we investigated whether the interaction of KIR3DS1 on primary NK cells with HLA-F on the HLA-null cell line 721.221 (221) stimulated KIR3DS1+ NK cells. We used a panel of Abs to detect KIR3DS1+ CD56dim NK cells that coexpressed the inhibitory NK cell receptors KIR2DL1/L2/L3, 3DL2, NKG2A, and ILT2; the activating NK cell receptors KIR2DS1/S2/S3/S5; and CCL4, IFN-γ, and CD107a functions...
May 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29737194/characterization-of-cellular-immune-responses-in-thai-individuals-with-and-without-hiv-associated-neurocognitive-disorders
#4
Silvia Ratto-Kim, Alexandra Schuetz, Pasiri Sithinamsuwan, John Barber, Nicholas Hutchings, Sukalaya Lerdlum, James L K Fletcher, Yuwadee Phuang-Ngern, Weerawan Chuenarom, Somporn Tipsuk, Mantana Pothisri, Tanate Jadwattanakul, Supunnee Jirajariyavej, Chayada Sajjaweerawan, Siriwat Akapirat, Thep Chalermchai, Duanghathai Suttichom, Boot Keawboon, Peeriya Prueksakaew, Putthachard Karnsomlap, David Clifford, Robert H Paul, Mark de Souza, Jerome H Kim, Jintinant Anaworanich, Victor Valcour
HIV-associated cognitive disorder (HAND) remains a challenge despite antiretroviral therapy (ART), and has been linked to monocyte/macrophage (M/M) migration to the brain. Due to the potential impact of T cell effector mechanisms in eliminating activated/HIV-infected M/M, T cell activation may play a role in the development of HAND. We sought to investigate the relationship between cognition and both CD8+ T-cell activation (HLA-DR+/CD38+) and HIV-specific CD8+ T-cell responses at the time of HIV diagnosis and 12 months post initiation of ART...
May 8, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29736145/functional-activity-of-natural-killer-cells-in-biological-fluids-in-patients-with-colorectal-and-ovarian-cancers
#5
Natalia V Yunusova, Marina N Stakheyeva, Sergey V Molchanov, Sergey G Afanas'ev, Anastasia A Tsydenova, Larisa A Kolomiets, Nadejda V Cherdyntseva
Aim of the study: To compare the functional activity of natural killer cells depending on the presence of a malignant process and its dissemination. Material and methods: The study included 20 patients with Stage IIIB, C (FIGO, 2009) ovarian cancer, 10 patients with benign ovarian tumours (BOT), and 20 patients with colorectal cancer (T2-4N0-2M0). The control group consisted of 9 healthy donors. To evaluate the number and functional activity of NK cells, multicolour flow cytometry was performed...
2018: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/29713652/natural-killer-cells-from-malignant-pleural-effusion-are-endowed-with-a-decidual-like-proangiogenic-polarization
#6
Annalisa Bosi, Silvia Zanellato, Barbara Bassani, Adriana Albini, Alessandra Musco, Maria Cattoni, Matteo Desio, Elisa Nardecchia, Davide Giuseppe D'Urso, Andrea Imperatori, Lorenzo Dominioni, Douglas M Noonan, Lorenzo Mortara, Antonino Bruno
Natural killer (NK) cells are crucial in tumor recognition and eradication, but their activity is impaired in cancer patients, becoming poorly cytotoxic. A particular type of NK cells, from the decidua, has low cytotoxicity and shows proangiogenic functions. We investigated whether NK cells from peripheral blood (PB) and pleural effusions of patients develop decidual-like NK phenotype and whether exposure to IL-2 can restore their killing ability in the presence of pleural fluids. NK cells from pleural effusion of patients with inflammatory conditions (iPE, n  = 18), primary tumor (ptPE, n  = 18), and metastatic tumor (tmPE, n  = 27) acquired the CD56bright CD16- phenotype...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29713323/implication-of-interleukin-12-15-18-and-ruxolitinib-in-the-phenotype-proliferation-and-polyfunctionality-of-human-cytokine-preactivated-natural-killer-cells
#7
Iñigo Terrén, Idoia Mikelez, Irati Odriozola, Andrea Gredilla, Javier González, Ane Orrantia, Joana Vitallé, Olatz Zenarruzabeitia, Francisco Borrego
A brief in vitro stimulation of natural killer (NK) cells with interleukin (IL)-12, IL-15, and IL-18 endow them a memory-like behavior, characterized by higher effector responses when they are restimulated after a resting period of time. These preactivated NK cells, also known as cytokine-induced memory-like (CIML) NK cells, have several properties that make them a promising tool in cancer immunotherapy. In the present study, we have described the effect that different combinations of IL-12, IL-15, and IL-18 have on the generation of human CIML NK cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29686681/-anaplasma-phagocytophilum-related-defects-in-cd8-nkt-and-nk-lymphocyte-cytotoxicity
#8
Diana G Scorpio, Kyoung-Seong Choi, J Stephen Dumler
Human granulocytic anaplasmosis, caused by the tick-transmitted Anaplasma phagocytophilum , is not controlled by innate immunity, and induces a proinflammatory disease state with innate immune cell activation. In A. phagocytophilum murine infection models, hepatic injury occurs with production of IFNγ thought to be derived from NK, NKT cells, and CD8 T lymphocytes. Specific A. phagocytophilum ligands that drive inflammation and disease are not known, but suggest a clinical and pathophysiologic basis strikingly like macrophage activation syndrome (MAS) and hemophagocytic syndrome (HPS)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29682590/hepatitis-b-vaccination-induced-tnf-%C3%AE-and-il-2-producing-t-cell-responses-in-hiv-healthy-individuals-higher-than-in-hiv-individuals-who-received-the-same-vaccination-regimen
#9
Kriangkrai Chawansuntati, Kanokporn Chaiklang, Romanee Chaiwarith, Jutarat Praparattanapan, Khuanchai Supparatpinyo, Jiraprapa Wipasa
We investigated cytokine production and expression of degranulation marker CD107a after different strategies of hepatitis B virus (HBV) vaccination in human immunodeficiency virus-infected individuals, which were three doses of 20  μ g (standard dose group), four doses of 20  μ g (four doses group), or four doses of 40  μ g (four double doses group), compared to standard dose vaccination in healthy controls. PBMCs collected at different time points were stimulated in vitro with recombinant hepatitis B surface antigen and analyzed by flow cytometry...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29621281/evidence-of-functional-cell-mediated-immune-responses-to-nontypeable-haemophilus-influenzae-in-otitis-prone-children
#10
Elke Seppanen, Dino Tan, Karli J Corscadden, Andrew J Currie, Peter C Richmond, Ruth B Thornton, Lea-Ann S Kirkham
Otitis media (OM) remains a common paediatric disease, despite advances in vaccinology. Susceptibility to recurrent acute OM (rAOM) has been postulated to involve defective cell-mediated immune responses to common otopathogenic bacteria. We compared the composition of peripheral blood mononuclear cells (PBMC) from 20 children with a history of rAOM (otitis-prone) and 20 healthy non-otitis-prone controls, and assessed innate and cell-mediated immune responses to the major otopathogen nontypeable Haemophilus influenzae (NTHi)...
2018: PloS One
https://www.readbyqxmd.com/read/29602251/tim-3-blockade-promotes-inkt-cell-function-to-inhibit-hbv-replication
#11
Yong Xu, Zehua Wang, Xianhong Du, Yuan Liu, Xiaojia Song, Tixiao Wang, Siyu Tan, Xiaohong Liang, Lifen Gao, Chunhong Ma
Increased expression of T cell immunoglobulin and mucin domain-3 (Tim-3) on invariant natural killer T (iNKT) cells is reported in chronic hepatitis B virus (HBV) infection. However, whether Tim-3 regulates iNKT cells in chronic HBV condition remains unclear. In this study, our results showed that the expression of Tim-3 was up-regulated on hepatic iNKT cells from HBV-transgenic (Tg) mice or iNKT cells stimulated with α-galactosylceramide (α-Galcer). Compared with Tim-3- iNKT cells, Tim-3+ iNKT cells expressed more IFN-γ, IL-4 and CD107a, indicating a strong relationship between Tim-3 and iNKT cell activation...
March 30, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29600283/zika-virus-infection-preferentially-counterbalances-human-peripheral-monocyte-and-or-nk-cell-activity
#12
Fok-Moon Lum, David Lee, Tze-Kwang Chua, Jeslin J L Tan, Cheryl Y P Lee, Xuan Liu, Yongxiang Fang, Bernett Lee, Wearn-Xin Yee, Natasha Y Rickett, Po-Ying Chia, Vanessa Lim, Yee-Sin Leo, David A Matthews, Julian A Hiscox, Lisa F P Ng
Zika virus (ZIKV) has reemerged in the population and caused unprecedented global outbreaks. Here, the transcriptomic consequences of ZIKV infection were studied systematically first in human peripheral blood CD14+ monocytes and monocyte-derived macrophages with high-density RNA sequencing. Analyses of the ZIKV genome revealed that the virus underwent genetic diversification, and differential mRNA abundance was found in host cells during infection. Notably, there was a significant change in the cellular response, with cross talk between monocytes and natural killer (NK) cells as one of the highly identified pathways...
March 2018: MSphere
https://www.readbyqxmd.com/read/29599759/emergence-of-cd4-and-cd8-polyfunctional-t-cell-responses-against-immunodominant-lytic-and-latent-ebv-antigens-in-children-with-primary-ebv-infection
#13
Janice K P Lam, K F Hui, Raymond J Ning, X Q Xu, K H Chan, Alan K S Chiang
Long term carriers were shown to generate robust polyfunctional T cell (PFC) responses against lytic and latent antigens of Epstein-Barr virus (EBV). However, the time of emergence of PFC responses against EBV antigens, pattern of immunodominance and difference between CD4+ and CD8+ T cell responses during various stages of EBV infection are not clearly understood. A longitudinal study was performed to assess the development of antigen-specific PFC responses in children diagnosed to have primary symptomatic (infectious mononucleosis [IM]) and asymptomatic (AS) EBV infection...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29587879/rituximab-impedes-natural-killer-cell-function-in-chronic-fatigue-syndrome-myalgic-encephalomyelitis-patients-a-pilot-in-vitro-investigation
#14
Natalie Eaton, Hélène Cabanas, Cassandra Balinas, Anne Klein, Donald Staines, Sonya Marshall-Gradisnik
BACKGROUND: A recent in vitro pilot investigation reported Rituximab significantly reduced natural killer (NK) cell cytotoxicity in healthy donors. Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown etiology. A consistent finding is a significant reduction in NK cell cytotoxicity. Rituximab has been reported having questionable potential therapeutic benefits for the treatment of CFS/ME, however, the potential effects of Rituximab on NK cell cytotoxicity in CFS/ME patients are yet to be determined...
March 27, 2018: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29566059/the-immunological-effect-of-galectin-9-tim-3-pathway-after-low-dose-mifepristone-treatment-in-mice-at-14-5-day-of-pregnancy
#15
Adrienn Lajko, Matyas Meggyes, Beata Polgar, Laszlo Szereday
The abortifacient Mifepristone (RU486) has proven to be a safe, effective, acceptable option for millions of women seeking abortion during the first and second trimester of pregnancy although its precise mechanism of action is not well understood. The main objective of this study was to investigate the impact of low dose Mifepristone administration on placental Galectin-9 (Gal-9) expression, as well as its effect on the cell surface expression of Gal-9, TIM-3 and CD107a molecules by different T and NK cell subsets...
2018: PloS One
https://www.readbyqxmd.com/read/29541698/adcc-mediated-cd56-dim-nk-cell-responses-are-associated-with-early-hbsag-clearance-in-acute-hbv-infection
#16
Wen-Han Yu, Cormac Cosgrove, Christoph T Berger, Patrick C Cheney, Marina Krykbaeva, Arthur Y Kim, Lia Lewis-Ximenez, Georg M Lauer, Galit Alter
Background: Hepatitis B virus (HBV) affects up to 400 million people worldwide and accounts for approximately one million deaths per year from liver pathologies. Current treatment regimens are effective in suppressing viremia but usually have to be taken indefinitely, warranting research into new therapeutic approaches. Acute HBV infection in adults almost universally results in resolution of viremia, with the exception of immunocompromised persons, suggesting that the immune response can functionally cure or even eradicate HBV infection...
2018: Pathogens & Immunity
https://www.readbyqxmd.com/read/29536036/human-cytomegalovirus-infection-increases-both-antibody-and-non-antibody-dependent-cellular-reactivity-by-natural-killer-cells
#17
Clive M Michelo, Bram van Cranenbroek, Peran Touw, Frans H J Claas, Arnold van der Meer, Irma Joosten
Background: Antibody-mediated rejection in solid organ transplantation is an important immunological barrier to successful long-term graft survival. Next to complement activation, natural killer (NK) cells have been implicated in the process. Human cytomegalovirus (CMV), independently associated with decreased graft survival, has a strong imprint on the immune response. Here, we assessed the effect of CMV status on alloreactive NK cell reactivity. Methods: We compared antibody-mediated NK cell cytolytic activity (CD107a expression) and IFNγ production between healthy CMV-seropositive (n = 8) and CMV-seronegative (n = 11) individuals, in cocultures of NK cells with anti-HLA class I or rituximab (control) antibody-coated Raji cells...
December 2017: Transplantation Direct
https://www.readbyqxmd.com/read/29534721/t-cell-mediated-immunity-induced-by-the-live-attenuated-shigella-flexneri-2a-vaccine-candidate-cvd-1208s-in-humans
#18
Franklin R Toapanta, Paula J Bernal, Karen L Kotloff, Myron M Levine, Marcelo B Sztein
BACKGROUND: Shigellosis persists as a public health problem worldwide causing ~ 165,000 deaths every year, of which ~ 55,000 are in children less than 5 years of age. No vaccine against shigellosis is currently licensed. The live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S (S. flexneri 2a; ΔguaBA, Δset, Δsen) demonstrated to be safe and immunogenic in phase 1 and 2 clinical trials. Earlier reports focused on humoral immunity. However, Shigella is an intracellular pathogen and therefore, T cell mediated immunity (T-CMI) is also expected to play an important role...
March 13, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29525609/differential-effect-of-dietary-vitamin-d-supplementation-on-natural-killer-cell-activity-in-lean-and-obese-mice
#19
Ga Young Lee, Chan Yoon Park, Kyeong Sun Cha, Seung Eun Lee, Munkyong Pae, Sung Nim Han
Vitamin D has an immunoregulatory effect on both innate and adaptive immunity. Contradictory results regarding vitamin D and natural killer (NK) cell functions have been reported with in vitro studies, but little is known about this in vivo. We investigated whether vitamin D levels (50, 1000 or 10,000 IU/kg of diet: DD, DC or DS) affect NK cell functions in mice fed a control or high-fat diet (10% or 45% kcal fat: CD or HFD) for 12 weeks. The splenic NK cell activity was significantly higher in the CD-DS group than the HFD-DS group, and the CD-DS group showed significantly higher NK cell activity compared with the CD-DD and CD-DC groups...
May 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29518421/mast-cell-activation-test-in-the-diagnosis-of-allergic-disease-and-anaphylaxis
#20
Rajia Bahri, Adnan Custovic, Peter Korosec, Marina Tsoumani, Martin Barron, Jiakai Wu, Rebekah Sayers, Alf Weimann, Monica Ruiz-Garcia, Nandinee Patel, Abigail Robb, Mohamed H Shamji, Sara Fontanella, Mira Silar, E N Clare Mills, Angela Simpson, Paul J Turner, Silvia Bulfone-Paus
BACKGROUND: Food allergy is an increasing public health issue and the most common cause of life-threatening anaphylactic reactions. Conventional allergy tests assess for the presence of allergen-specific IgE, significantly overestimating the rate of true clinical allergy and resulting in overdiagnosis and adverse effect on health-related quality of life. OBJECTIVE: To undertake initial validation and assessment of a novel diagnostic tool, we used the mast cell activation test (MAT)...
March 5, 2018: Journal of Allergy and Clinical Immunology
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