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NK cell memory

Qing Zhang, Jiacheng Bi, Xiaodong Zheng, Yongyan Chen, Hua Wang, Wenyong Wu, Zhengguang Wang, Qiang Wu, Hui Peng, Haiming Wei, Rui Sun, Zhigang Tian
Checkpoint blockade enhances effector T cell function and has elicited long-term remission in a subset of patients with a broad spectrum of cancers. TIGIT is a checkpoint receptor thought to be involved in mediating T cell exhaustion in tumors; however, the relevance of TIGIT to the dysfunction of natural killer (NK) cells remains poorly understood. Here we found that TIGIT, but not the other checkpoint molecules CTLA-4 and PD-1, was associated with NK cell exhaustion in tumor-bearing mice and patients with colon cancer...
June 18, 2018: Nature Immunology
Evidio Domingo-Musibay, Paari Murugan, Alessio Giubellino, Sandeep Sharma, Daniel Steinberger, Jianling Yuan, Matthew A Hunt, Emil Lou, Jeffrey S Miller
BACKGROUND: Sebaceous carcinoma is an aggressive adnexal skin tumor with a predilection for the eyelids and sebaceous glands of the head and neck. CASE PRESENTATION: A 73 year-old man presented with confusion and was found to have widely disseminated sebaceous carcinoma with metastases to brain, lungs, liver, bowel, lymph nodes, and bone. Following initial treatment of the brain metastases with surgery he received post-operative radiosurgery. He then began systemic immunotherapy with pembrolizumab...
June 19, 2018: Journal for Immunotherapy of Cancer
Becker Meng-Po Law, Ray Wilkinson, Xiangju Wang, Katrina Kildey, Mae Lindner, Kenneth Beagley, Helen Healy, Andrew J Kassianos
Background: γδ T cells are effector lymphocytes recognized as key players during chronic inflammatory processes. Mouse studies suggest a pathological role for γδ T cells in models of kidney disease. Here we evaluated γδ T cells in human native kidneys with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Methods: γδ T cells were extracted from human kidney tissue and enumerated and phenotyped by multicolour flow cytometry...
April 20, 2018: Nephrology, Dialysis, Transplantation
Heather M McGee, Megan E Daly, Sohelia Azghadi, Susan L Stewart, Leslie Oesterich, Jeffrey Schlom, Renee Donahue, Jonathan D Schoenfeld, Qian Chen, Shyam Rao, Ruben C Fragoso, Richard K Valicenti, Robert J Canter, Emmanual M Maverakis, William J Murphy, Karen Kelly, Arta M Monjazeb
PURPOSE: Despite the strong interest in combining stereotactic ablative radiation therapy (SAR) with immunotherapy, limited data characterizing the systemic immune response after SAR are available. We hypothesized that the systemic immune response to SAR would differ by irradiated site owing to inherent differences in the microenvironment of various organs. METHODS AND MATERIALS: Patients receiving SAR to any organ underwent prospective blood banking before and 1 to 2 weeks after SAR...
April 22, 2018: International Journal of Radiation Oncology, Biology, Physics
Frédéric Vély, Vincent Barlogis, Evelyne Marinier, Marie-Edith Coste, Béatrice Dubern, Emmanuelle Dugelay, Julie Lemale, Christine Martinez-Vinson, Noël Peretti, Ariane Perry, Patrice Bourgeois, Catherine Badens, Olivier Goulet, Jean-Pierre Hugot, Catherine Farnarier, Alexandre Fabre
The syndromic diarrhea/trichohepatoenteric syndrome (SD/THE) is a rare and multi-system genetic disorder caused by mutation in SKIV2L or in TTC37 , two genes encoding subunits of the putative human SKI complex involved in RNA degradation. The main features are intractable diarrhea of infancy, hair abnormalities, facial dysmorphism, and intrauterine growth restriction. Immunologically this syndrome is associated with a hypogammaglobulinemia leading to an immunoglobulin supplementation. Our immune evaluation of a large French cohort of SD/THE patient revealed several immunological defects...
2018: Frontiers in Immunology
Cristina Capuano, Simone Battella, Chiara Pighi, Lavinia Franchitti, Ombretta Turriziani, Stefania Morrone, Angela Santoni, Ricciarda Galandrini, Gabriella Palmieri
Natural killer (NK) cells represent a pivotal player of innate anti-tumor immune responses. The impact of environmental factors in shaping the representativity of different NK cell subsets is increasingly appreciated. Human cytomegalovirus (HCMV) infection profoundly affects NK cell compartment, as documented by the presence of a CD94/NKG2C+ FcεRIγ- long-lived "memory" NK cell subset, endowed with enhanced CD16-dependent functional capabilities, in a fraction of HCMV-seropositive subjects. However, the requirements for memory NK cell pool establishment/maintenance and activation have not been fully characterized yet...
2018: Frontiers in Immunology
Peter J Darlington, Brandon Stopnicki, Tarik Touil, Jean-Sebastien Doucet, Lama Fawaz, Morgan E Roberts, Marie-Noëlle Boivin, Nathalie Arbour, Mark S Freedman, Harold L Atkins, Amit Bar-Or
In autoimmunity, the balance of different helper T (Th) cell subsets can influence the tissue damage caused by autoreactive T cells. Pro-inflammatory Th1 and Th17 T cells are implicated as mediators of several human autoimmune conditions such as multiple sclerosis (MS). Autologous hematopoietic stem cell transplantation (aHSCT) has been tested in phase 2 clinical trials for MS patients with aggressive disease. Abrogation of new clinical relapses and brain lesions can be seen after ablative aHSCT, accompanied by significant reductions in Th17, but not Th1, cell populations and activity...
2018: Frontiers in Immunology
Daniel R Ram, Cordelia Manickam, Brady Hueber, Hannah L Itell, Sallie R Permar, Valerie Varner, R Keith Reeves
Natural killer (NK) cells classically typify the nonspecific effector arm of the innate immune system, but have recently been shown to possess memory-like properties against multiple viral infections, most notably CMV. Expression of the activating receptor NKG2C is elevated on human NK cells in response to infection with CMV as well as HIV, and may delineate cells with memory and memory-like functions. A better understanding of how NKG2C+ NK cells specifically respond to these pathogens could be significantly advanced using nonhuman primate (NHP) models but, to date, it has not been possible to distinguish NKG2C from its inhibitory counterpart, NKG2A, in NHP because of unfaithful antibody cross-reactivity...
May 31, 2018: PLoS Pathogens
Moritz Rapp, Gabriela M Wiedemann, Joseph C Sun
Natural killer (NK) cells are classified as innate immune cells, given their ability to rapidly respond and kill transformed or virally infected cells without prior sensitization. Recently, accumulating evidence suggests that NK cells also exhibit many characteristics similar to cells of the adaptive immune system. Analogous to T cells, NK cells acquire self-tolerance during development, express antigen-specific receptors, undergo clonal-like expansion, and can become long-lived, self-renewing memory cells with potent effector function providing potent protection against reappearing pathogens...
May 28, 2018: Seminars in Immunopathology
Mahyar Nouri-Shirazi, Saba Tamjidi, Erika Nourishirazi, Elisabeth Guinet
The magnitude of immune responses to vaccination is a critical factor in determining protection from disease. It is known that cigarette smoke dampens the immune system and increases the risk of vaccine-preventable diseases. We reported that nicotine, the immunosuppressive component of cigarette smoke, disrupts the differentiation and functional properties of DC, which are pivotal in the initiation of immune response to vaccines. We also reported that TLR agonists act in synergy and boost DC maturation, DC-NK crosstalk and ultimately naïve T cell polarization into effector Th1 and Tc1 cells...
May 24, 2018: International Immunopharmacology
Abner A Murray, Chao Wang, Steven Fiering, Nicole F Steinmetz
Cancer immunotherapy approaches have emerged as novel treatment regimens against cancer. A particularly interesting avenue is the concept of in situ vaccination, where immunostimulatory agents are introduced into an identified tumor to overcome local immunosuppression and, if successful, mount systemic antitumor immunity. We had previously shown that nanoparticles from cowpea mosaic virus (CPMV) are highly potent in inducing long-lasting antitumor immunity when used as an in situ vaccine in various tumor mouse models...
May 25, 2018: Molecular Pharmaceutics
Antonio Cassone
Trained immunity was originally proposed as a program of innate immunity memory by innate immunity cells of hematopoietic origin such as the monocytes/macrophages and the NK cells. Here I discuss some old and new data justifying this program and some specific, still unanswered, questions it raises regarding the model fungus Candida albicans and the chronic, inflammatory vulvovaginal disease it causes. Building upon this well-established program, the recent reports that epithelial cells of mammals can also acquire memory from previous stimulations, and the apparent intrinsic ability of many living cells from bacteria to mammals to learn from experience, I suggest an expansion of the concept of trained immunity to include all cells of different lineages with the potential of memorizing previous microbial encounters...
May 22, 2018: MBio
Guro Kristin Melve, Elisabeth Ersvaer, Geir Egil Eide, Einar K Kristoffersen, Øystein Bruserud
Background: Allogeneic hematopoietic stem cell transplantation is associated with a high risk of immune-mediated post-transplant complications. Graft depletion of immunocompetent cell subsets is regarded as a possible strategy to reduce this risk without reducing antileukemic immune reactivity. Study design and methods: We investigated the effect of hematopoietic stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) on peripheral blood and stem cell graft levels of various T, B, and NK cell subsets in healthy donors...
2018: Frontiers in Immunology
Kamel Laribi, Mustapha Alani, Catherine Truong, Alix Baugier de Materre
OBJECTIVE: Mature T-cell lymphomas are a heterogeneous group of T-cell malignancies with a poor outcome. The discovery of new molecular biomarkers has led to the emergence of new drugs in recent years that target various signaling pathways. METHOD: We examined all pertinent published patents through 2015 that analyzed novel methods for the diagnosis and treatment of T cell lymphoma, as well as related published and unpublished studies. Selection criteria were established before data collection...
May 16, 2018: Recent Patents on Anti-cancer Drug Discovery
Moriya Gamliel, Debra Goldman-Wohl, Batya Isaacson, Chamutal Gur, Natan Stein, Rachel Yamin, Michael Berger, Myriam Grunewald, Eli Keshet, Yoach Rais, Chamutal Bornstein, Eyal David, Adam Jelinski, Iris Eisenberg, Caryn Greenfield, Arbel Ben-David, Tal Imbar, Ronit Gilad, Ronit Haimov-Kochman, David Mankuta, Matan Elami-Suzin, Ido Amit, Jacob H Hanna, Simcha Yagel, Ofer Mandelboim
Natural killer cells (NKs) are abundant in the human decidua, regulating trophoblast invasion and angiogenesis. Several diseases of poor placental development are associated with first pregnancies, so we thus looked to characterize differences in decidual NKs (dNKs) in first versus repeated pregnancies. We discovered a population found in repeated pregnancies, which has a unique transcriptome and epigenetic signature, and is characterized by high expression of the receptors NKG2C and LILRB1. We named these cells Pregnancy Trained decidual NK cells (PTdNKs)...
May 15, 2018: Immunity
Kornelis S M van der Geest, Bart-Jan Kroesen, Gerda Horst, Wayel H Abdulahad, Elisabeth Brouwer, Annemieke M H Boots
Immune-aging is associated with perturbed immune responses in the elderly. CD161-expressing T cells, i.e., the previously described subsets of CD161+ CD4+ T cells, CD161high CD8+ T cells, and CD161int CD8+ T cells, are highly functional, pro-inflammatory T cells. These CD161-expressing T cells are critical in immunity against microbes, while possibly contributing to autoimmune diseases. So far, little is known about the impact of aging on the frequency, phenotype, and function of these CD161-expressing T cells...
2018: Frontiers in Immunology
John R Heckenlively, Steven K Lundy
Autoimmune retinopathy (AIR) was often mistaken for retinitis pigmentosa (RP), due to an overlap of clinical findings, but increasingly has been recognized as a unique entity in the last decade. AIR has distinctive features: sudden onset of photopsias and scotomata in patients with no family history of RP, followed by visual field and central vision loss. Initially, retina exams are normal with no sign of pigment deposits or retinal degeneration. A family history of autoimmune diseases (all types) occurs in 60% of patients...
2018: Advances in Experimental Medicine and Biology
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
Nicolas Jouand, Céline Bressollette-Bodin, Nathalie Gérard, Magali Giral, Pierrick Guérif, Audrey Rodallec, Romain Oger, Tiphaine Parrot, Mathilde Allard, Anne Cesbron-Gautier, Nadine Gervois, Béatrice Charreau
Immune response against human cytomegalovirus (HCMV) includes a set of persistent cytotoxic NK and CD8 T cells devoted to eliminate infected cells and to prevent reactivation. CD8 T cells against HCMV antigens (pp65, IE1) presented by HLA class-I molecules are well characterized and they associate with efficient virus control. HLA-E-restricted CD8 T cells targeting HCMV UL40 signal peptides (HLA-EUL40) have recently emerged as a non-conventional T-cell response also observed in some hosts. The occurrence, specificity and features of HLA-EUL40 CD8 T-cell responses remain mostly unknown...
April 30, 2018: PLoS Pathogens
Erin C Zook, Zhong-Yin Li, Yiying Xu, Renée F de Pooter, Mihalis Verykokakis, Aimee Beaulieu, Anna Lasorella, Mark Maienschein-Cline, Joseph C Sun, Mikael Sigvardsson, Barbara L Kee
All innate lymphoid cells (ILCs) require the small helix-loop-helix transcription factor ID2, but the functions of ID2 are not well understood in these cells. We show that mature natural killer (NK) cells, the prototypic ILCs, developed in mice lacking ID2 but remained as precursor CD27+ CD11b- cells that failed to differentiate into CD27- CD11b+ cytotoxic effectors. We show that ID2 limited chromatin accessibility at E protein binding sites near naïve T lymphocyte-associated genes including multiple chemokine receptors, cytokine receptors, and signaling molecules and altered the NK cell response to inflammatory cytokines...
April 27, 2018: Science Immunology
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