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Nathan Goodyear

Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunolog... - 0 views

edrv.endojournals.org/...44.full

natural killer cells pregnancy loss recurrent immune system miscarriage NK

shared by Nathan Goodyear on 15 Apr 12 - No Cached
  • NK cells have been the cells most extensively studied, primarily because they constitute the predominant leukocyte population present in the endometrium at the time of implantation and in early pregnancy
  • parental chromosomal abnormalities, uterine anatomic anomalies, endometrial infections, endocrine etiologies (luteal phase defect, thyroid dysfunction, uncontrolled diabetes mellitus), antiphospholipid syndrome, inherited thrombophilias, and alloimmune causes
  • estrogen
  • ...28 more annotations...
  • progesterone
  • prolactin
  • In summary, in vivo animal experiments have shown an inhibitory role of estrogen on peripheral NK cell lytic activity, which is partly due to suppression of NK cell output by the bone marrow and partly due to suppression of individual NK cell cytotoxicity. However, in vitro studies so far have failed to show conclusively a direct effect of estrogen on NK cells.
  • At the progesterone concentrations believed to be present in the uterus [up to 10−5 m at the maternal-fetal interface (35)], studies consistently show inhibition of lymphocyte proliferation (33) and inhibition of NK cytolytic activity in vitro
  • The exact role of prolactin in NK cell regulation is unknown.
  • The overall effects of estrogen on NK cells are likely multifactorial, therefore, and depend on the type of cell affected as well as the kind of ER expressed by that cell.
  • It is known that progesterone can directly affect T cell differentiation in vitro, suppressing development of the Th1 pathway and enhancing differentiation along the Th2 pathway (44)
  • Th1 cells predominantly produce interferon-γ (IFN-γ), IL-2, and TNF-β and are involved in cell-mediated immunity. Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13 and stimulate humoral immunity
  • Furthermore, in response to progesterone, γδ T cells produce progesterone-induced blocking factor (PIBF) (54
  • A defining characteristic of NK cells is their ability to lyse target cells without prior sensitization and without restriction by HLA antigens.
  • NK cell function is mainly regulated by IL-2 and IFN-γ
  • IL-2 causes both NK cell proliferation and enhanced cytotoxicity. IFN-γ augments NK cytolytic activity, but does not cause NK proliferation. The two cytokines act synergistically to augment NK cytotoxicity (6).
  • The largest leukocyte population in the endometrium consists of NK cells named large granulated lymphocytes
  • there is a significant increase in the number of uNK cells throughout the secretory phase, which peaks in early pregnancy when uNK cells comprise about 75% of uterine leukocytes (62)
  • Second, uNK cell phenotype changes during the normal menstrual cycle and early pregnancy (68)
  • general proinflammatory effect of estrogen, causing an influx of macrophages and neutrophils, which is antagonized by progesterone through its receptor (70, 71).
  • The mechanism of such a progesterone-induced local immunosuppression is unclear.
  • progesterone plays an important role in proliferation and differentiation of uNK cells (32).
  • Through promotion of a uterine Th2 environment, progesterone could indirectly affect uNK cell function
  • The mechanism of this increase in uNK cell numbers has been addressed in both human and mouse models, and is likely the result of: 1) recruitment of peripheral NK cells to the uterus, and 2) proliferation of existing uNK cells
  • prolactin system plays an important role in implantation and the maintenance of pregnancy
  • the exact pathways of hormonal regulation of NK cells remain to be delineated.
  • The exact function of uNK cells has not yet been unequivocally determined
  • uNK cells express a different cytokine profile, compared with resting peripheral NK cells. mRNAs for granulocyte CSF, M-CSF, GM-CSF, TNF-α, IFN-γ, TGF-β, and leukemia inhibitory factor (LIF) have been found in decidual CD56+ cells
  • Their increased numbers in early pregnancy, their hormonal dependence, and their close proximity to the infiltrating trophoblast all suggest that they play an important role in the regulation of the maternal immune response to the fetal allograft and the control of trophoblast growth and invasion during human pregnancy
  • role of uNK cell-derived cytokines on trophoblast growth and differentiation (114, 115, 116, 117).
  • Th1 immunity to trophoblast is associated with RPL, whereas Th2 immunity is associated with a successful pregnancy
  • RPL is associated with Th1 immunity, for which NK cells are partly responsible.
  • Nathan Goodyear on 15 Apr 12
     
    dysregulated immune system plays role in recurrent miscarriage.  Specifically, this article discusses natural killer cells (NK).
Nathan Goodyear

Interleukin‐2 enhances the natural killer cell response to Herceptin‐coated H... - 1 views

onlinelibrary.wiley.com/...%3AAID-IMMU3016%3E3.0.CO%3B2-J

IL-2 breast cancer cancer NK cells HER-2 immunotherapy

shared by Nathan Goodyear on 18 Jun 18 - No Cached
  • administration of low‐dose IL‐2 results in expansion of a CD3– / CD56+ NK cell population in patients with advanced cancer
  • approximately 20 % will overexpress theHer2 / neu proto‐oncogene
  • In breast cancer, Her2 / neu overexpression is associated with a worse histologicalgrade, decreased relapse‐free and overall survival periods, and altered sensitivity to chemotherapeutic regimens
  • ...17 more annotations...
  • NK cells are large granular lymphocytes that comprise approximately 10 % of circulating lymphocytes
  • all human NK cells express the CD56 antigen
  • treatment with various concentrations of IL‐2 in vivo may induce distinct functions within the NK cell compartment and, therefore, may have profound effects on NK cell‐mediated cytotoxicity
  • CD56bright
  • CD56dim
  • We show here that ADCC conducted by NK cells in vitro is enhanced by IL‐2 activation and is critically dependent on interactions between FcγRIII on NK cells and Herceptin‐coated tumor targets
  • administration of low‐dose IL‐2 to patients results in the marked expansion of a CD56+ population of immune effectors with the ability to lyse antibody‐coated cancer targets
  • NK cells represented only 7 % of lymphocytes prior to therapy but comprised over 50 % of the population after 10 weeks of low‐dose IL‐2
  • These data suggest that the enhanced ADCC seen following the expansion of NK cells with low‐dose IL‐2 is likely due to an increase in the overall number of NK cells
  • co‐administration of IL‐2 with rhu4D5 mAb will enhance activation of NK cell effector functions
  • Stimulation of NK cells with IL‐2 resulted in a significant increase in the lysis of rhu4D5‐coated targets
  • We have shown that costimulation with IL‐2 plus rhu4D5 results in significant production of IFN‐γ by NK cells with concomitant up‐regulation of cell‐surface activation and adhesion molecules
  • It has been previously demonstrated that continuous low‐dose IL‐2 can expand a CD56+ lymphocyte population, and we have now shown that this cell population is a potent mediator of ADCC against rhu4D5 mAb‐coated Her2 / neu+ targets
  • These results suggest that administration of low‐dose IL‐2 can be used to expand NK cell numbers, while higher doses may be used to enhance their cytolytic capacity in the setting of mAb therapy
  • we have demonstrated that NK cell lysis of Her2 / neu+ breast cancer cell lines in the presence of rhu4D5 mAb is markedly enhanced following stimulation with IL‐2
  • we have presented evidence that administration of low‐dose IL‐2 in vivo results in the expansion of a potent NK cell effector population
  • Our experiments suggest that NK cells costimulated with IL‐2 and immobilized IgG can secrete potent immunomodulatory cytokines which may serve to potentiate the anti‐tumor immune response.
  • Nathan Goodyear on 18 Jun 18
     
    low dose IL-2 found to expand NK levels in conjuction in with herceptin in HER-2 positive breast cancer cell lines.
Nathan Goodyear

Activation of NK cells by extracellular heat shock protein 70 through induction of NKG2... - 0 views

www.ncbi.nlm.nih.gov/...PMC2935777

heat shock proteins NK cells natural killer cells cancer

shared by Nathan Goodyear on 29 Sep 18 - No Cached
  • Heat shock proteins (HSPs) are intracellular molecular chaperones that play essential roles in facilitating protein folding
  • their ability to interact with APCs and to chaperone antigenic peptides for cross-presentation to MHC class I and class II molecules on APC
  • vaccination with HSP70 was associated with increased T cell, as well as NK cell, activity in patients with CML
  • ...6 more annotations...
  • HSP70 did not activate NK cells directly. Instead, HSP70 induced the expression of an NKG2D ligand MICA on DCs, which then activated NK cells in an NKG2D-dependent manner.
  • DCs are the most powerful professional antigen presenting cells (APCs) that are instrumental in processing antigens and orchestrating antigen-specific adaptive immunity and tolerance
  • NK cells and DCs can functionally interact with each other both in vitro and in vivo
  • autologous HSP70 could stimulate significant IFN-γ production
  • The magnitude of the IFN-γ response was different from patient to patient and correlated with the number of functional NK cells
  • In addition, 10 out of 14 patients had significantly increased IFN-γ producing cells in the peripheral blood after HSP70 vaccinations, which is again in line with increased NK cell activity as reported in our original study in these patients
  • Nathan Goodyear on 29 Sep 18
     
    great review of the relationship between heat shock proteins and NK cells.
Nathan Goodyear

Histamine dihydrochloride and low-dose interleukin-2 as post-consolidation im... - 0 views

www.academia.edu/...rapy_in_acute_myeloid_leukemia

AML leukemia acute myeloid leukemia IL-2 histamine cancer NK cells

shared by Nathan Goodyear on 31 May 18 - No Cached
  • IL-2 is a central T cell-derived cytokine, which induces NK cell and T cell proliferation, differentiation and activation, and also stim-ulates the production of secondary immunostimulatory cytokines
  • combination of histamine and IL-2 thus triggers efficient NK cell-mediated killing of several types of leukemic cells, including freshly recovered human AML blasts
  • histamine improves the effects of IL-2 on T cell activation
  • ...3 more annotations...
  • principal action of histamine is to protect cytotoxic lymphocytes from myeloid-cell-induced inactivation, thus improving the efficiency of the T and NK cell stimulation achieved by IL-2
  • random-ized Phase II study of patients with renal cell carcinoma further support the suggestion that the combination of HDC and IL-2 improves lymphocyte functions
  • HDC improves the effectiveness of IL-2-induced T and NK cell activation in cancer patients, as predicted in preclinical models
  • Nathan Goodyear on 31 May 18
     
    histamine dihydrochloride enhances immune effects of NK cells in IL02 therapy; specifically in this analysis in AML, the histamin prevented inactivation of the IL-2 activated NK cells.
Nathan Goodyear

Molecular Control of Immune/Inflammatory Responses: Interactions Between Nucl... - 0 views

edrv.endojournals.org/...435.long

progesterone NK macrophage T cell activity inflammation immune system

shared by Nathan Goodyear on 09 Nov 12 - No Cached
  • Nathan Goodyear on 09 Nov 12
     
    Benefits of progesterone, are in part, due to its function on the immune system.  Progesterone shown to decrease T cell activity, macrophage activity and NK cell activity.  Aside, NK cell activity has been found to be increased in those with recurrent first trimester miscarriages and progesterone defects.  So, low progesterone allows for a rise in NK cell activity and inflammation that is detrimental to a developing pregnancy.  If that is the case in pregnancy, what about the rest of the body?
Nathan Goodyear

Mistletoe viscotoxins increase natural killer cell‐mediated cytotoxicity - Ta... - 0 views

febs.onlinelibrary.wiley.com/...j.1432-1033.2002.02932.x

cancer mistletoe NK NK cells

shared by Nathan Goodyear on 08 Jul 18 - No Cached
  • Nathan Goodyear on 08 Jul 18
     
    Study finds that mistletoe augments NK activity not via an increase in NK numbers.
Nathan Goodyear

(PDF) Mistletoe Extract Reduces the Surgical Suppression of Natural Killer Cell Activit... - 0 views

www.researchgate.net/...s_A_Randomized_Phase_III_Trial

mistletoe NK NK cells cancer

shared by Nathan Goodyear on 08 Jul 18 - No Cached
  • Nathan Goodyear on 08 Jul 18
     
    Phase III study finds that IV mistletoe reversed operative NK suppressio pointed to the increase NK effect of mistletoe.
Nathan Goodyear

Adjuvant histamine in cancer immunotherapy, Seminars in Cancer Biology | 10.1006/scbi.2... - 0 views

www.deepdyve.com/...ancer-immunotherapy-6XEaCggcvx

histamine IL-2 NK NK cells immunotherapy cancer

shared by Nathan Goodyear on 12 May 18 - No Cached
  • Nathan Goodyear on 12 May 18
     
    histamine dihydrochloride augments IL-2 stimulation of NK and blocks the monocyte/macrophage inhibition of IL-2 stimulation of NK cells.
Nathan Goodyear

Effects of Hyperthermia on the Host Immune System : From NK Cell-based Science to Clini... - 0 views

www.jstage.jst.go.jp/...en

NK cells hyperthermia immunotherapy

shared by Nathan Goodyear on 19 Feb 21 - No Cached
  • Nathan Goodyear on 19 Feb 21
     
    Immunotherapy augments internal NK cells and NK cell therapy.
Nathan Goodyear

Studies on activity of... [J Huazhong Univ Sci Technolog Med Sci. 2004] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...15641696

preeclampsia NK cell immune tolerance pregnancy recurrent miscarriage miscarriages

shared by Nathan Goodyear on 19 Apr 12 - No Cached
  • Nathan Goodyear on 19 Apr 12
     
    As NK over activity has been shown to play in role in recurrent miscarriages, so it appears that loss if immune tolerance (elevated NK activity) may play a role in preeclampsia
Nathan Goodyear

Uterine and circulating natural killer cell... [J Reprod Immunol. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21632120

RPL recurrent pregnancy loss NK immunology immune system natural killer cells preeclampsia pre-eclampsia PIH

shared by Nathan Goodyear on 19 Apr 12 - No Cached
  • Nathan Goodyear on 19 Apr 12
     
    women with RPL and preeclampsia carry same immunologic NK abnormalities.  Loss of immune tolerance, elevated maternal NK, shown to play role in both.
Nathan Goodyear

Angiogenic Factors and Natural Killer (NK) Cells in the Pathogenesis of Preeclampsia - 0 views

www.ncbi.nlm.nih.gov/...PMC2147723

natural killer cells pregnancy preeclampsia pre-eclampsia RPL

shared by Nathan Goodyear on 20 Apr 12 - No Cached
  • Nathan Goodyear on 20 Apr 12
     
    Abnormal NK cell activity in the placenta plays a likely role in the development of preeclampsia. This proposes an immunologic role in the development of preeclampsia.  This process is similar to the literatures link between maternal NK and RPL.
Nathan Goodyear

The role of decidual natural killer ce... [J Obstet Gynaecol Can. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18611298

preeclampsia pre-eclampsia NK cell natural killer RPL recurrent pregnancy loss

shared by Nathan Goodyear on 20 Apr 12 - No Cached
  • Nathan Goodyear on 20 Apr 12
     
    same NK link to RPL, linked to preeclampsia.  NK cells play important role in the development of the spiral arteries in the placenta. It has long been thought, that the placenta was the likely culprit in the development of preeclampsia
Nathan Goodyear

CD56bright natural killer (NK) cells: an important NK cell subset - 0 views

www.ncbi.nlm.nih.gov/...PMC2673358

natural killer cells NK cells

shared by Nathan Goodyear on 28 Sep 18 - No Cached
  • Nathan Goodyear on 28 Sep 18
     
    Good review of CD16/56 cell subpopulation of NK cells.
Nathan Goodyear

Effect of ozone therapy on T-lymphocyte subsets,NK cell in the patients with ... - 0 views

en.cnki.com.cn/...CJFDTOTAL-SXYX200703007.htm

Ozone cancer lymphoma NK cells NK immunotherapy

shared by Nathan Goodyear on 02 Nov 18 - No Cached
  • Nathan Goodyear on 02 Nov 18
     
    Ozone therapy appears to support NK cell and other immune cells when used in conjunction with chemotherapy versus chemotherapy alone in the treatment of lymphoma
Nathan Goodyear

Histamine: A Novel Approach to Cancer Immunotherapy: Cancer Investigation: Vol 18, No 4 - 0 views

www.tandfonline.com/...07357900009012178

histamine NK IL-2 cancer immunotherapy

shared by Nathan Goodyear on 12 May 18 - No Cached
  • Nathan Goodyear on 12 May 18
     
    histamin augments NK activation with IL-2 therapy. Histamine blocks the monocyte/macrophate inhibition of IL-2 induced NK activity.
Nathan Goodyear

Hyperthermia as an immunotherapy strategy for cancer - 1 views

www.ncbi.nlm.nih.gov/...PMC2828267

cancer hyperthermia

shared by Nathan Goodyear on 29 Nov 18 - No Cached
  • the notion of treating human cancers with heat dates back to the writings of Hippocrates
  • enhance the efficiency of standard cancer therapies, such as chemotherapy and radiation treatment
  • After antigen uptake at tumor sites, APCs have the ability to create a robust response by entering lymphoid compartments and programming lymphocytes
  • ...36 more annotations...
  • Hyperthermia differs fundamentally from fever in that it elevates the core body temperature without changing the physiological set point
  • hyperthermia is induced by increasing the heat load and/or inactivating heat dissipation
  • mor cells [2]. Although significant cell killing could be achieved by heating cells or tissues to temperatures > 42°C for 1 or more hours, the application, measurement and consistency of this temperature range within the setting of cancer clinical trials
  • mild temperature hyperthermia (ie, within the fever-range, 39–41°C)
    • Nathan Goodyear
      Nathan Goodyear on 04 Aug 19
       
      101.2 to 105.8
  • moderate hyperthermia (41°C)
    • Nathan Goodyear
      Nathan Goodyear on 04 Aug 19
       
      105.8 F
  • Hsps are a family of stress-induced proteins
  • they are key regulators of cellular protein activity, turnover and trafficking
  • Hsps ensure appropriate post-translational protein folding, and are able to refold denatured proteins, or mark irreversibly damaged proteins for destruction
  • the ability of fever-range hyperthermia to induce reactive immunity against tumor antigens through DCs and NK-cells is likely mediated by Hsps
  • thermotolerance
  • Hsps support the malignant phenotype of cancer cells by not only affecting the cells’ survival, but also participating in angiogenesis, invasion, metastasis and immortalization mechanisms
  • Hsps released from stressed or dying cells activate dendritic cells (DCs), transforming them into mature APCs
  • In theory, fever-range hyperthermia may take advantage of tumor cell Hsps by inducing their release from tumor cells and augmenting DC priming against tumor antigens
  • In several models of hyperthermia, heat-treated tumors exhibited improved DC priming and generation of systemic immunity to tumor cell
  • hyperthermia alone can enhance antigen display by tumor cells, thus rendering them even more susceptible to programmed immune clearance
  • Fever-range hyperthermia may also induce Hsps
  • Hsps may exert an adjuvant effect by bolstering MHC class II and co-stimulatory molecule expression by DCs
  • thermal ablation of liver tumors in particular has demonstrated an ability to potentiate immune responses [57, 58] and elicit robust T-cell infiltrates at ablation sites
  • specific Hsp, Hsp70, directly inhibits apoptosis pathways in cancer cells, as demonstrated in human pancreatic, prostate and gastric cancer cells
  • Cross-priming is the ability of extracellular Hsps complexed to tumor peptides to be internalized and presented in the context of MHC class I molecules on APCs, thus allowing potent priming of CTLs against tumor antigens
  • It has been reported that Hsps are generated from necrotic tumor cell lysates, but not from tumor cells undergoing apoptosis
  • tumor cells exposed to hyperthermia in the heat shock range (42°C for 4h) prior to lysing, DC activation and cross-priming were significantly enhanced with the application of heat
  • Due to the ability of Hsps to activate DCs directly by chaperoning tumor antigens upon their release [28], it is possible that both local and regional immune stimulation can be achieved with hyperthermia.
  • support the use of hyperthermia as an inducer of Hsps to serve as ‘danger signals’, activating antitumor immune responses
  • whole-body hyperthermia not only augments immune responses, but also stimulates the migration of skin-derived DCs to draining lymph nodes
    • Nathan Goodyear
      Nathan Goodyear on 04 Aug 19
       
      This allows for the activation of lymphocytes by the activated dendritic cells.
  • suggest a valuable role of hyperthermia in DC cancer vaccine strategies
  • In mice treated with fever-range whole-body hyperthermia, tumor growth was significantly inhibited and NK-cell infiltration increased
    • Nathan Goodyear
      Nathan Goodyear on 04 Aug 19
       
      Hyperthermia increased NK cell activation, proliferation, and infiltration, which equals increased cytotoxicity.
  • exposure to fever-range hyperthermia resulted in improved endogenous NK-cell cytotoxicity to several cancer types
  • improved activation and function of DCs and NK cells following hyperthermia
  • Hyperthermia increases the expression ICAM-1 a key adhesion molecule,
  • The combined effects of hyperthermia on lymphoid tissue endothelium and lymphocytes can promote immune surveillance and increase the probability of naive lymphocytes leaving the circulation and encountering their cognate antigen displayed by DCs in lymphoid organs.
  • In independent clinical studies, whole-body hyperthermia resulted in a transient decrease in circulating lymphocytes in patients with advanced cancer [12, 94, 99, 100], a finding which mirrored observations in animal models in which lymphocyte entry into lymph noeds was increased following hyperthermia treatment [93]. Enhanced recruitment of lymphocytes to lymphoid tissues may be exploited in the treatment of malignancies.
  • The initial tumor antigen presentation and initiation of clonal expansion of CTLs transpires in the lymph nodes and cannot take place outside this specialized compartment
  • the ability of DCs present in the lymph nodes to stimulate an anti-tumor immune response is critical
  • hyperthermia has been shown to improve immune surveillance by T-cell
  • and to increase DC trafficking to lymph nodes
  • Nathan Goodyear on 29 Nov 18
     
    Great review of hyperthermia.
Nathan Goodyear

Regulatory NK-Cell Functions in Inflammation and Autoimmunity - 0 views

www.ncbi.nlm.nih.gov/...PMC2710290

NK natural killer inflammation autoimmune autoimmune disease autoimmunity

shared by Nathan Goodyear on 04 Feb 13 - No Cached
  • Nathan Goodyear on 04 Feb 13
     
    good review on NK cell role in inflammation and autoimmune disease
Nathan Goodyear

NK cells in autoimmunity: a two-edg'd weapon o... [Autoimmun Rev. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18486926

natural killer NK autoimmune autoimmune disease autoimmunity

shared by Nathan Goodyear on 04 Feb 13 - No Cached
  • Nathan Goodyear on 04 Feb 13
     
    NK cells play role in autoimmune disease.
Nathan Goodyear

NK cells and pre-eclampsia. [Reprod Biomed Online. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18284877

NK cells preeclampsia pre-eclampsia PIH

shared by Nathan Goodyear on 19 Apr 12 - No Cached
  • Nathan Goodyear on 19 Apr 12
     
    NK cells and their role in pre-eclampsia
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