819 research outputs found
Natural killer cells and neuroblastoma: Tumor recognition, escape mechanisms, and possible novel immunotherapeutic approaches
No full textNeuroblastoma (NB) is the most common extra-cranial solid tumor of childhood and arises from developing sympathetic nervous system. Most primary tumors localize in the abdomen, the adrenal gland, or lumbar sympathetic ganglia. Amplification in tumor cells of MYCN, the major oncogenic driver, patients' age over 18 months, and the presence at diagnosis of a metastatic disease (stage IV, M) identify NB at high risk of treatment failure. Conventional therapies did not significantly improve the overall survival of these patients. Moreover, the limited landscape of somatic mutations detected in NB is hampering the development of novel pharmacological approaches. Major efforts aim to identify novel NB-associated surface molecules that activate immune responses and/or direct drugs to tumor cells and tumor-associated vessels. PVR (Poliovirus Receptor) and B7-H3 are promising targets, since they are expressed by most high-risk NB, are upregulated in tumor vasculature and are essential for tumor survival/invasiveness. PVR is a ligand of DNAM-1 activating receptor that triggers the cytolytic activity of natural killer (NK) cells against NB. In animal models, targeting of PVR with an attenuated oncolytic poliovirus induced tumor regression and elimination. Also B7-H3 was successfully targeted in preclinical studies and is now being tested in phase I/II clinical trials. B7-H3 down-regulates NK cytotoxicity, providing NB with a mechanism of escape from immune response. The immunosuppressive potential of NB can be enhanced by the release of soluble factors that impair NK cell function and/or recruitment. Among these, TGF-β1 modulates the cytotoxicity receptors and the chemokine receptor repertoire of NK cells. Here, we summarize the current knowledge on the main cell surface molecules and soluble mediators that modulate the function of NK cells in NB, considering the pros and cons that must be taken into account in the design of novel NK cell-based immunotherapeutic approaches. © 2014 Bottino, Dondero, Bellora, Moretta, Locatelli, Pistoia, Moretta and Castriconi
Roberts, Infant Child of Moretta, Death Certificate, 1915
No full textDeath certificate for the infant child of Moretta Roberts.
Age: 2 days
Death Date: February 26, 1915
Cause: Congenital malformation
Burial Date: February 27, 1915
Location: Zion Cemetery, Tampa, Hillsborough County, Florida
Father: C. W. Venrance of Nassau, Bahamas
Mother: Moretta Kneelly of Nassau, Bahamas
Undertaker: F. G. Gree
Management of relapsed acute lymphoblastic leukemia in childhood with conventional and innovative approaches
No full textTo review and summarize the available evidence on factors predicting prognosis of children with relapsed acute lymphoblastic leukemia (ALL) and on the currently used treatment strategies, as well as on the most promising and innovative molecular or cellular therapies
Human NK cells: from HLA class I‐specific killer Ig‐like receptors to the therapy of acute leukemias
No full textActivating and inhibitory killer immunoglobulin-like receptors (KIR) in haploidentical haemopoietic stem cell transplantation to cure high-risk leukaemias.
No full textA number of experimental studies have shown that natural killer (NK) cells can eliminate cancer cells and the mechanisms involved in this effect have been uncovered during the last two decades. Clinical data from haploidentical haematopoietic stem cell transplantation (haplo-HSCT) revealed that NK cells were responsible for remarkably favourable effects in both adult and
paediatric high-risk leukaemias.NK receptors specific for major histocompatibility complex (MHC) class I molecules, including killer immunoglobulin (Ig)-like receptors (KIR) and CD94/NKG2A, play a major role in the antileukaemia effect (mediating either inhibitory or activating signals). Haplo-HSCT requires a heavy conditioning regimen for the patient and the use of large numbers of T cell-depleted HSC to be grafted. After transplantation, natural killer cells develop from HSC shortly after engraftment and may
include ‘alloreactive’ NK cells that kill leukaemic cells and prevent graftversus-host disease (GvHD). Alloreactive NK cells are characterized by the expression of KIR that are not engaged by any of the human leucocyte antigen (HLA) class I alleles expressed by the patient. Their generation is dependent upon the existence of a KIR/HLA class I mismatch between donor and
recipient. Novel important information on the function and specificity of different KIR has been obtained recently by the analysis of donor-derived alloreactive NK cells in a cohort of paediatric patients given haplo-HSCT to cure acute, high-risk leukaemias
Haploidentical haematopoietic stem cell transplantation: Role of NK cells and effect of cytomegalovirus infections
No full textNatural killer cells play an important role in the immune responses against cancer and viral infections. In addition, NK cells have been shown to exert a key role in haploidentical hematopoietic stem cell (HSC) transplantation for the therapy of high-risk leukemias. The anti-leukemia effect is mostly related to the presence of “alloreactive” NK cells, i.e., mature KIR+ NK cells that express inhibitory KIR mismatched with HLA class I (KIR-L) of the patient. In addition, an important role is played by certain activating KIR (primarily, but not only, KIR2DS1) upon interaction with their HLA class I ligand (C2 alleles). In general, the presence of activating KIR correlates with a better prognosis. Beside the infusion of “pure” CD34+ cells, a novel protocol has been recently developed in which depletion of αβ T cells and CD19+ B cells makes it possible to infuse into the patient, together with donor CD34+ HSCs, important effector cells including mature PB NK cells and γδ T cells. Recent studies revealed that cytomegalovirus (CMV) infection/reactivation may induce rapid NK cell maturation and greatly influence the NK receptor repertoire. The remarkable expansion of a subset expressing the activating receptor NKG2C, together with a more efficient virus-specific effector response after rechallenge with CMV (i.e., antigen specificity), and the longevity of the expanded population are all features consistent with an adaptive type of response and support the notion of a memory-like activity of NK cells
Killer Ig-like receptors (kirs). their role in nk cell modulation and developments leading to their clinical exploitation
No full textNatural killer (NK) cells contribute to the first line of defense against viruses and to the control of tumor growth and metastasis spread. The discovery of HLA class I specific inhibitory receptors, primarily of killer Ig-like receptors (KIRs), and of activating receptors has been fundamental to unravel NK cell function and the molecular mechanisms of tumor cell killing. Stemmed from the seminal discoveries in early ‘90s, in which Alessandro Moretta was the major actor, an extraordinary amount of research on KIR specificity, genetics, polymorphism, and repertoire has followed. These basic notions on NK cells and their receptors have been successfully translated to clinical applications, primarily to the haploidentical hematopoietic stem cell transplantation to cure otherwise fatal leukemia in patients with no HLA compatible donors. The finding that NK cells may express the PD-1 inhibitory checkpoint, particularly in cancer patients, may allow understanding how anti-PD-1 therapy could function also in case of HLA class Ineg tumors, usually susceptible to NK-mediated killing. This, together with the synergy of therapeutic anti-checkpoint monoclonal antibodies, including those directed against NKG2A or KIRs, emerging in recent or ongoing studies, opened new solid perspectives in cancer therapy
Mathematical and Statistical Approaches for Anaerobic Digestion Feedstock Optimization
No full textThis book examines biomass mixture modeling and optimization.
The book discusses anaerobic digestion and related fermentative processes and explains their compositional dynamics. Early chapter examine macromolecules, elemental fractions, and their direct influence on methane production. Supported by an extensive data bank of substrates obtained from research, the book points out correlations that enable the estimation of global methane production for diverse biomass mixtures. Furthermore, it provides valuable insights into discerning the optimal composition capable of yielding the utmost methane output.
The book integrates cutting-edge machine learning techniques and shows how the programming language Python and Julia can be used for analysis and to optimize processes. It has many graphs, figures, and visuals
Innate lymphoid cells in normal and disease: An introductory overview
No full textInnate lymphoid cells (ILC) represent a novel group of lymphocytes that, different from T and B-lymphocytes lack recombinant activating genes (RAG-1 or RAG-2) and thus do not express rearranged antigen-specific receptors. Members of this family, i.e. NK cells, have been known since long time, while the other ILCs have been discovered only in recent years, possibly because of their predominant localization in tissues, primarily in mucosal tissues, skin and mucosa-associated lymphoid organs. ILC have been grouped in three major subsets on the basis of their phenotypic and functional features as well as of their dependency on given transcription factors (TF). Briefly, ILC-1 are dependent on T-bet TF and produce interferon (IFN)-γ. Group 2 ILC (ILC2) express GATA-3 TF and produce IL-5, IL-4 and IL-13 (Type 2) cytokines while group 3 ILC (ILC3) express RORγt TF and produce IL-17 and IL-22. ILC provide early defenses against pathogens and intervene in the repair of damaged tissues. ILC activation is mediated by cytokines (specifically acting on different ILC groups) and/or by activating receptors that are, at least in part, the same that had been previously identified in NK cells
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