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https://www.readbyqxmd.com/read/29029499/generation-and-characterization-of-erbb2-car-engineered-cytokine-induced-killer-cells-for-the-treatment-of-high-risk-soft-tissue-sarcoma-in-children
#1
Michael Merker, Verena Pfirrmann, Sarah Oelsner, Simone Fulda, Thomas Klingebiel, Winfried S Wels, Peter Bader, Eva Rettinger
Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma (STS) who are simultaneously showing signs of cumulative treatment toxicity are in need of novel therapies. In this preclinical analysis, we identified ErbB2 as a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells transduced with the lentiviral 2(nd)-generation chimeric antigen receptor (CAR) vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets with the CD3(+) T cell phenotype showed up to 85% cell surface expression of the respective CAR...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29018171/dual-enhancement-of-t-and-nk-cell-function-by-pulsatile-inhibition-of-ship1-improves-antitumor-immunity-and-survival
#2
Matthew Gumbleton, Raki Sudan, Sandra Fernandes, Robert W Engelman, Christopher M Russo, John D Chisholm, William G Kerr
The success of immunotherapy in some cancer patients has revealed the profound capacity for cytotoxic lymphocytes to eradicate malignancies. Various immunotherapies work by blocking key checkpoint proteins that suppress immune cell activity. The phosphatase SHIP1 (SH2-containing inositol polyphosphate 5-phosphatase) limits signaling from receptors that activate natural killer (NK) cells and T cells. However, unexpectedly, genetic ablation studies have shown that the effector functions of SHIP1-deficient NK and T cells are compromised in vivo...
October 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28986438/decidual-t-cells-exhibit-a-highly-differentiated-phenotype-and-demonstrate-potential-fetal-specificity-and-a-strong-transcriptional-response-to-ifn
#3
Richard M Powell, David Lissauer, Jennifer Tamblyn, Andrew Beggs, Philip Cox, Paul Moss, Mark D Kilby
Immune tolerance during human pregnancy is maintained by a range of modifications to the local and systemic maternal immune system. Lymphoid infiltration is seen at the implantation site of the fetal-maternal interface, and decidual NK cells have been demonstrated to facilitate extravillous trophoblast invasion into maternal decidua during the first trimester, optimizing hemochorial placentation. However, although there is considerable T cell infiltration of the maternal decidua, the functional properties of this T cell response remain poorly defined...
October 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28955346/natural-killer-cell-memory-progress-and-implications
#4
REVIEW
Hui Peng, Zhigang Tian
Immunological memory is a cardinal feature of adaptive immunity. Although natural killer (NK) cells have long been considered short-lived innate lymphocytes that respond rapidly to transformed and virus-infected cells without prior sensitization, accumulating evidence has recently shown that NK cells develop long-lasting and antigen-specific memory to haptens and viruses. Additionally, cytokine stimulation alone can induce memory-like NK cells with longevity and functional competence, leading to emerging interest in harnessing NK cell memory for cancer immunotherapy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28947538/phenotypic-and-functional-characterization-of-circulatory-splenic-and-hepatic-nk-cells-in-simian-immunodeficiency-virus-controlling-macaques
#5
Diego A Vargas-Inchaustegui, Sabrina Helmold Hait, Hye Kyung Chung, Jigna Narola, Tanya Hoang, Marjorie Robert-Guroff
NK cells are key components of the immune system because of their rapid response potential and their ability to mediate cytotoxic and immunomodulatory functions. Additionally, NK cells have recently been shown to persist for long periods in vivo and to have the capacity to establish immunologic memory. In the current study, we assessed the phenotype and function of circulatory and tissue-resident NK cells in a unique cohort of SIV-controlling rhesus macaques that maintained low to undetectable levels of viremia in the chronic phase of infection...
September 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28935847/cd56bright-nk-regulatory-cells-in-filgrastim-primed-donor-blood-or-marrow-products-regulate-chronic-gvhd-cbmtg-randomized-0601-study-results
#6
Amina Kariminia, Sabine Ivison, Bernard Ng, Jacob Rozmus, Susanna Sung, Avani Varshney, Mahmoud Aljurf, Silvy Lachance, Irwin Walker, Cindy Toze, Jeff Lipton, Stephanie J Lee, Jeff Szer, Richard Doocey, Ian Lewis, Clayton Smith, Naeen Chaudhri, Megan K Levings, Raewyn Broady, Gerald Devins, David Szwajcer, Ronan Foley, Sara Mostafavi, Steven Pavletic, Donna A Wall, Stephen Couban, Tony Panzarella, Kirk R Schultz
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease...
September 21, 2017: Haematologica
https://www.readbyqxmd.com/read/28932639/soluble-nkg2d-ligands-in-the-ovarian-cancer-microenvironment-are-associated-with-an-adverse-clinical-outcome-and-decreased-memory-effector-t-cells-independent-of-nkg2d-downregulation
#7
Maulik Vyas, Silke Reinartz, Nathalie Hoffmann, Katrin S Reiners, Sonja Lieber, Julia M Jansen, Uwe Wagner, Rolf Müller, Elke Pogge von Strandmann
The immune receptor NKG2D is predominantly expressed on NK cells and T cell subsets and confers anti-tumor activity. According to the current paradigm, immune surveillance is counteracted by soluble ligands shed into the microenvironment, which down-regulate NKG2D receptor expression. Here, we analyzed the clinical significance of the soluble NKG2D ligands sMICA and sULBP2 in the malignancy-associated ascites of ovarian cancer. We show that high levels of sMICA and sULBP2 in ascites were associated with a poor prognosis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28926127/recall-features-and-allorecognition-in-innate-immunity
#8
REVIEW
Hirofumi Uehara, Koichiro Minami, Markus Quante, Yeqi Nian, Timm Heinbokel, Haruhito Azuma, Abdala El Khal, Stefan G Tullius
Alloimmunity traditionally distinguishes short-lived, rapid and non-specific innate immune responses from adaptive immune responses that are characterized by a highly specific response initiated in a delayed fashion. Key players of innate immunity such as natural killer (NK) cells and macrophages present the first-line defense of immunity. The concept of unspecific responses in innate immunity has recently been challenged. The discovery of pattern recognition receptors (PRRs) has demonstrated that innate immune cells respond in a semi-specific fashion through the recognition of pathogen-associated molecular patterns (PAMPs) representing conserved molecular structures shared by large groups of microorganisms...
September 19, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28920584/liver-resident-nk-cells-and-their-potential-functions
#9
Hui Peng, Rui Sun
Natural killer (NK) cells represent a heterogeneous population of innate lymphocytes with phenotypically and functionally distinct subsets. In particular, recent studies have identified a unique subset of NK cells residing within the liver that are maintained as tissue-resident cells, confer antigen-specific memory responses and exhibit different phenotypical and developmental characteristics compared with conventional NK (cNK) cells. These findings have encouraged researchers to uncover tissue-resident NK cells at other sites, and detailed analyses have revealed that these tissue-resident NK cells share many similarities with liver-resident NK cells and tissue-resident memory T cells...
September 18, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28898397/genome-wide-dna-methylation-analysis-of-senescence-in-repetitively-infected-memory-ctls-dna-methylation-analysis-of-repetitively-infected-memory-ctls
#10
Jumpei Shosaku
The immune system including antigen-specific CD8 T cells, which are cytotoxic T lymphocytes (CTLs), can acquire the potential of more effective elimination of the pathogen for reinfection. Since memory CTLs could exert protective immunity after the next response, we aimed to elucidate the substantial change of repetitively infected memory CTLs. Currently, DNA methylation status in repetitively infected memory CTLs is still unknown. Therefore, we performed next generation sequencing (NGS) to evaluate methylation status and transcriptional regulation of naive, primary and secondary memory CD8 T cells on the basis of transcription start sites (TSS)...
September 12, 2017: Immunology
https://www.readbyqxmd.com/read/28893282/development-of-targeted-adjuvants-for-hiv-1-vaccines
#11
REVIEW
Jun Liu, Mario Ostrowski
Finding new adjuvants is an integrated component of the efforts in developing an effective HIV-1 vaccine. Compared with traditional adjuvants, a modern adjuvant in the context of HIV-1 prevention would elicit a durable and potent memory response from B cells, CD8(+) T cells, and NK cells but avoid overstimulation of HIV-1 susceptible CD4(+) T cells, especially at genital and rectal mucosa, the main portals for HIV-1 transmission. We briefly review recent advances in the studies of such potential targeted adjuvants, focusing on three classes of molecules that we study: TNFSF molecules, TLRs agonists, and NODs agonists...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28888485/immunobiology-of-the-il-15-il-15r%C3%AE-complex-as-an-antitumor-and-antiviral-agent
#12
REVIEW
Yin Guo, Liming Luan, Naeem K Patil, Edward R Sherwood
Interleukin (IL)-15 is essential for natural killer (NK), NKT and memory (m) CD8(+) T cell development and function, and is currently under investigation as an immunotherapeutic agent for the treatment of cancer. Recently, the creation of IL-15 superagonist by complexing IL-15 and its high affinity receptor alpha (IL-15 Rα) in solution, inspired by the natural trans-presentation of IL-15, advances the potential of IL-15-based tumor immunotherapy. IL-15 superagonist shows promising advantages over monomeric IL-15 such as sustaining high circulating concentrations due to prolonged half-life and more potently stimulating NK and CD8(+) T effector lymphocytes...
September 1, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28863960/memory-responses-of-natural-killer-cells
#13
REVIEW
Clair D Geary, Joseph C Sun
Natural killer (NK) cells have traditionally been classified as a cellular component of the innate immune system, given their ability to rapidly produce effector cytokines and kill infected or transformed cells without prior exposure. More recently, NK cells have been shown to possess features of adaptive immunity such as clonal expansion, longevity, and robust recall responses. NK cell memory can be broadly divided into two categories: antigen-specific and antigen-independent. In the first case, exposure to certain viral or hapten stimuli endows NK cells with antigen-specific immunological memory, similar to T and B cells...
August 30, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28855906/memory-of-natural-killer-cells-a-new-chance-against-mycobacterium-tuberculosis
#14
REVIEW
José Alberto Choreño Parra, Nayeli Martínez Zúñiga, Luis Antonio Jiménez Zamudio, Luis Armando Jiménez Álvarez, Citlaltepetl Salinas Lara, Joaquín Zúñiga
Natural killer (NK) cells are lymphocytes of the innate immune system, which play an important role in the initial defense against a wide variety of pathogens, including viruses and intracellular bacteria. NK cells produce cytokines that enhance immune responses directed toward pathogens and also exert cytotoxic activity against infected cells, thereby eliminating the reservoir of infection. Their role in defense against Mycobacterium tuberculosis (Mtb) has been recently studied, and there is increasing evidence that highlight the importance of NK cell function during pulmonary tuberculosis (PTB), especially in the absence of optimal T-cell responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28839507/comparison-of-immune-responses-in-pigs-infected-with-chinese-highly-pathogenic-prrs-virus-strain-hv-and-north-american-strain-nadc-20
#15
X Li, A Galliher-Beckley, L Wang, J Nietfeld, W Feng, J Shi
INTRODUCTION: Chinese HP-PRRSV characterized by high morbidity and mortality of all ages of pigs emerged since 2006 in China. The immune response of HP-PRRSV was never compared with conventional low pathogenic PRRSV strain. OBJECTIVE: In this study, we compared the immune responses elicited by a Chinese HP-PRRSV strain HV and a North American RRSV strain NADC20 infections. RESULT: Pigs infected with NADC-20 showed significantly higher Ab titers than HV-PRRSV infected pigs at 9 DPI...
2017: Open Virology Journal
https://www.readbyqxmd.com/read/28815218/capturing-the-systemic-immune-signature-of-a-norovirus-infection-an-n-of-1-case-study-within-a-clinical-trial
#16
Antony J Cutler, Joao Oliveira, Ricardo C Ferreira, Ben Challis, Neil M Walker, Sarah Caddy, Jia Lu, Helen E Stevens, Deborah J Smyth, Marcin L Pekalski, Jane Kennet, Kara M D Hunter, Ian Goodfellow, Linda S Wicker, John A Todd, Frank Waldron-Lynch
BACKGROUND:  The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28794018/redefining-memory-building-the-case-for-adaptive-nk-cells
#17
REVIEW
Silke Paust, Catherine A Blish, R Keith Reeves
Classically, natural killer (NK) cells have been defined by nonspecific innate killing of virus-infected and tumor cells. However, burgeoning evidence suggests that the functional repertoire of NK cells is far more diverse than has been previously appreciated, thus raising the possibility that there may be unexpected functional specialization and even adaptive capabilities among NK cell subpopulations. Some of the first evidence that NK cells respond in an antigen-specific fashion came from experiments revealing that subpopulations of murine NK cells were able to respond to a specific murine cytomegalovirus (MCMV) protein and that in the absence of T and B cells, murine NK cells also mediated adaptive immune responses to a secondary challenge with specific haptens...
October 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28791125/nkg2c-memory-like-nk-cells-contribute-to-the-control-of-hiv-viremia-during-primary-infection-optiprim-anrs-147
#18
Françoise Gondois-Rey, Antoine Chéret, Samuel Granjeaud, Françoise Mallet, Ghislain Bidaut, Camille Lécuroux, Mickaël Ploquin, Michaela Müller-Trutwin, Christine Rouzioux, Véronique Avettand-Fenoël, Alessandro Moretta, Gilles Pialoux, Cécile Goujard, Laurence Meyer, Daniel Olive
Natural-killer (NK) cells are important immune effectors during a viral infection. Latent CMV infection is widely spread and was demonstrated to shape the NK cell repertoire through the NKG2C receptor. An expansion of NKG2C(+) NK cells has been reported during primary HIV infection (PHI), but their role is not known. We previously found a correlation between the maturation state of the NK cell compartment and a lower viral load by studying patients from the ANRS 147 Optiprim trial. We investigated here extensively the NKG2C(+) NK cells at the time of PHI and its evolution after 3 months of early antiretroviral therapy (combination antiretroviral therapy (cART))...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28781750/natural-killer-cells-in-herpesvirus-infections
#19
REVIEW
Christian Münz, Obinna Chijioke
Natural killer (NK) cells are potent innate cytotoxic lymphocytes for the destruction of infected and transformed cells. Although they were originally considered to be ready-made assassins after their hematopoietic development, it has recently become clear that their activity is regulated by mechanisms such as repertoire composition, licensing, priming, and adaptive memory-like differentiation. Some of these mechanisms are influenced by infectious disease agents, including herpesviruses. In this review, we will compare expansion, stimulation, and effector functions of NK cell populations after infections with β- and γ 1-herpesviruses because, though closely related, these pathogens seem to drive completely opposite NK cell responses...
2017: F1000Research
https://www.readbyqxmd.com/read/28780374/maternal-t-and-b-cell-engraftment-in-two-cases-of-x-linked-severe-combined-immunodeficiency-with-igg1-gammopathy
#20
Tsubasa Okano, Takuro Nishikawa, Eri Watanabe, Takashi Watanabe, Takehiro Takashima, Tzu-Wen Yeh, Motoi Yamashita, Mari Tanaka-Kubota, Satoshi Miyamoto, Noriko Mitsuiki, Masatoshi Takagi, Yoshifumi Kawano, Yoshiki Mochizuki, Kohsuke Imai, Hirokazu Kanegane, Tomohiro Morio
X-linked severe combined immunodeficiency (X-SCID), caused by defects in the common gamma chain, is typically characterized by T and NK cell defects with the presence of B cells. T cell dysfunction and impaired class-switch recombination of B cells mean that patients typically have defects in class-switched immunoglobulins (IgG, IgA, and IgE) with detectable IgM. Here, we describe two patients with X-SCID with IgG1 gammopathy, in whom we identified maternal T and B cell engraftment. Exclusively, maternal B cells were found among the IgD(-)CD27(+) class-switched memory B cells, whereas the patients' B cells remained naïve...
August 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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