Immunology and Immunotherapy of Endometriosis

Endometriosis is one of the most common gynecological and systemic diseases, with a remarkable immune background. Patients suffer from pain and fertility reduction. Due to the distinct immune component, an immunotherapeutic approach may gain importance in the future. In endometriosis, shifts in the cell fractions of the immune system are well known. Moreover, hypoxia concomitant with inflammation causes a disturbed immune response. The removal of endometriosis has a therapeutic effect, normalizes the immune disorders, and remains the most effective causative treatment in terms of pain and infertility. A key issue is whether a similar effect can be achieved for fertility with non-invasive immunotherapy where surgery is inadvisable or cannot be performed for various reasons. Numerous immunotherapy trials, including vaccines, were conducted on animals only, although the research is encouraging. Among the promising methods of non-specific immunotherapy is the administration of an ethiodized oil contrast. Moreover, due to the significant successes of immunotherapy in oncology, the possibility of immunotherapy affecting NK cells has been postulated. NK cells are responsible for the surveillance and apoptosis of ectopic cells. Expanding the arsenal of endometriosis treatment by immunotherapy is promising due to the significant contribution of immunological factors and the limitations of current treatment methods.

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Modern possibilities for the diagnosis of adenomyosis

Journal of obstetrics and women s diseases ◽

10.17816/jowd18983 ◽

2021 ◽

Author(s):

Maria Shalina

Keyword(s):

Pathogenetic Mechanisms ◽

Non Invasive ◽

Immunological Factors

The article presents modern data on the diagnosis and pathogenetic mechanisms of the development of adenomyosis. Various classifications of the disease are highlighted. The role of genetic and immunological factors in the development of internal endometriosis is reflected. The results of domestic and foreign studies are presented and the most informative non-invasive markers for the diagnosis of adenomyosis are described.

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Role of natural killer cells in reproductive failure

Journal of obstetrics and women s diseases ◽

10.17816/jowd663143-156 ◽

2017 ◽

Vol 66 (3) ◽

pp. 143-156

Author(s):

Alana O. Agnaeva ◽

Olesya N. Bespalova ◽

Dmitriy I. Sokolov ◽

Sergey A. Selkov ◽

Igor Yu. Kogan

Keyword(s):

Nk Cells ◽

Peripheral Blood ◽

Recurrent Miscarriage ◽

Communication Process ◽

Modern World ◽

Unknown Etiology ◽

Sharp Change ◽

Reproductive Losses ◽

Immunological Factors

Reproductive losses are quite frequent in the modern world. They include: infertility, infertility of unknown etiology, multiple losses when IVF, recurrent implantation failure, miscarriage, recurrent miscarriage, both in the natural cycle and after ART management. It is important to note that the classification of some of these categories are not established yet. The etiology of reproductive losses is extremely diverse. Successful development of pregnancy at early terms is determined by genetic and immunological factors. Among the reproductive failures of unclear etiology, immunological causes are 50-80%. Over the past 20 years there are already known many different immunological factors that play role in the processes of fertilization. In this case, the evidence base on the role of each of them in the pathogenesis of reproductive failures is only being formed. Currently, the immunological relationship between mother and fetus is considered as a two-way communication process: the presentation of fetal antigens on the one hand, and on the other – the recognition and response to these antigens of the maternal immune system. Implantation of the embryo is accompanied by an increase in the production of proinflammatory cytokines followed by a sharp change in the cellular composition in the decidualizing endometrium, and the main population is NK cells. That is why this type of cells have a significant role in the normal development of pregnancy. The properties of NK cells in the uterus and peripheral blood are significantly different. To predict the onset and prolongation of pregnancy, peripheral blood NK (activity and quantity) is used. Evaluation of endometrial NK is often performed for the diagnosis of chronic endometritis. Currently, the definition of NK cells in peripheral blood in many clinics is proposed as a useful diagnostic test to address the issue of further appointment of immunoglobulins and evaluating the effectiveness of this therapy in patients with reproductive losses.

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Prospects for NK Cell Therapy of Sarcoma

Cancers ◽

10.3390/cancers12123719 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3719

Author(s):

Mieszko Lachota ◽

Marianna Vincenti ◽

Magdalena Winiarska ◽

Kjetil Boye ◽

Radosław Zagożdżon ◽

...

Keyword(s):

Nk Cells ◽

Molecular Mechanisms ◽

Cell Function ◽

Nk Cell ◽

Immune Surveillance ◽

Current Treatment ◽

Lymphoid Cells ◽

Current Evidence ◽

Treatment Regimens ◽

Novel Therapeutic Strategies

Natural killer (NK) cells are innate lymphoid cells with potent antitumor activity. One of the most NK cell cytotoxicity-sensitive tumor types is sarcoma, an aggressive mesenchyme-derived neoplasm. While a combination of radical surgery and radio- and chemotherapy can successfully control local disease, patients with advanced sarcomas remain refractory to current treatment regimens, calling for novel therapeutic strategies. There is accumulating evidence for NK cell-mediated immunosurveillance of sarcoma cells during all stages of the disease, highlighting the potential of using NK cells as a therapeutic tool. However, sarcomas display multiple immunoevasion mechanisms that can suppress NK cell function leading to an uncontrolled tumor outgrowth. Here, we review the current evidence for NK cells’ role in immune surveillance of sarcoma during disease initiation, promotion, progression, and metastasis, as well as the molecular mechanisms behind sarcoma-mediated NK cell suppression. Further, we apply this basic understanding of NK–sarcoma crosstalk in order to identify and summarize the most promising candidates for NK cell-based sarcoma immunotherapy.

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Increased NK Cells and Decreased CD3+CD8+CD62L+ T Cells in CML Patients Who Sustained Complete Molecular Remission After Discontinuation of Imatinib

Blood ◽

10.1182/blood.v118.21.1697.1697 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1697-1697

Author(s):

Kazuma Ohyashiki ◽

Sei-ichiro Katagiri ◽

Tetsuzo Tauchi ◽

Junko H Ohyashiki ◽

Yasuhiro Maeda ◽

...

Keyword(s):

Nk Cells ◽

Nk Cell ◽

Cell Activity ◽

Imatinib Therapy ◽

Imatinib Treatment ◽

Nk Cell Activity ◽

Normal Range ◽

Molecular Remission ◽

Circulating Lymphocytes ◽

Cell Fractions

Abstract Abstract 1697 Background and Aim: Recent study demonstrated that approximately 60% of chronic myeloid leukemia (CML) patients who stopped imatinib therapy (STOP-IM) after a period of stable complete molecular remission (CMR) relapsed molecularly within the next 6 months, whereas nearly all the remaining patients sustained a stable CMR beyond 18 months of follow-up. Study design: To elucidate the immunological diversity of CML patients, we assessed subsets of circulating lymphocytes obtained from 30 CML patients: 16 CML patients who had discontinued imatinib treatment for more than 6 months (STOP-IM), and 14 CML patients who were receiving imatinib with CMR for more than 2 consecutive years. Results: One-way analysis of variance revealed that certain cell fractions of lymphocyte subsets were significantly altered in STOP-IM patients compared with healthy volunteers and CML-CMR patients. We focused on the CD3+CD8+CD62L+ and CD3―CD56+ cell fractions, because other cell fractions, except CD19+CD20+, were not particularly different between STOP-IM and CML-CMR patients. The CD3+CD8+CD62L+ cell fractions in STOP-IM patients tended to down-regulate (P = 0.0658) and the CD3―CD56+ cell fraction increased significantly compared with that in CML-CMR (P = 0.0214). Our observations indicate that some lymphocyte subsets may be affected by imatinib therapy, even in CMR. The differences in subset cell fractions between CML-CMR and STOP-IM patients therefore may have some bearing on discontinuation of imatinib therapy. We were able to determine NK cell activity in 11 STOP-IM patients. This activity ranged from 24% to 69% (normal range, 18%–40%); 7 of the 11 patients had elevated NK cell activity, and a positive correlation was found between NK cell activity and NK cell percentages in the 11 STOP-IM patients. Discussion: We noticed deviation in some fractions of circulating lymphocytes in STOP-IM patients with CML, in comparison with CML patients who were CMR but were still taking imatinib. in STOP-IM patients in our study, an elevated cell fraction was detected only in CD3−CD56+ NK cells, and others were down-regulated. We were able to determine NK cell activity in 11 STOP-IM patients. This activity ranged from 24% to 69% (normal range, 18%–40%); 7 of the 11 patients had elevated NK cell activity, and a positive correlation was found between NK cell activity and NK cell percentages in the 11 STOP-IM patients. Two CMR patients satisfied criteria for both down-regulated CD3+CD8+CD62L+ cells and up-regulated CD3―CD56+ NK cells compared with those of healthy subjects. Conclusion: Our results therefore may aid in the selection of possible candidates for discontinuation of imatinib therapy in patients in CMR. The minimal requirements for discontinuation of imatinib treatment might be CMR duration of more than 2 years and low/intermediate Sokal scores at the time of CML diagnosis. In addition, increasing number of NK cells and decreased CD3+CD8+CD62L+ cell fractions may also be indications that imatinib therapy can be stopped. Disclosures: No relevant conflicts of interest to declare.

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ADCC-Mediated CD56dim NK Cell Responses Are Associated with Early HBsAg Clearance in Acute HBV Infection

Pathogens and Immunity ◽

10.20411/pai.v3i1.228 ◽

2018 ◽

Vol 3 (1) ◽

pp. 2 ◽

Cited By ~ 5

Author(s):

Wen-Han Yu ◽

Cormac Cosgrove ◽

Christoph T. Berger ◽

Patrick C. Cheney ◽

Marina Krykbaeva ◽

...

Keyword(s):

Nk Cells ◽

Nk Cell ◽

Acute Infection ◽

Cell Subset ◽

Current Treatment ◽

Hbv Infection ◽

Functional Studies ◽

Cell Responses ◽

Hbsag Clearance ◽

Cell Profile

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. Because immunophenotypic and functional studies have implicated a role for Natural Killer (NK) cells in HBV clearance during acute infection, we hypothesized that a distinct NK-cell profile exists in acute HBV infection that could provide information for the mechanism of HBV clearance. Using multivariate flow cytometry, we evaluated the expression of key activating and inhibitory receptors on NK cells, and their ability to respond to classic target cell lines. Multivariate analysis revealed selective perturbation of the CD56 dim NK-cell subset during acute infection, displaying low levels of NKp46+, NKp30+, CD160+ and CD161+ cells. Intriguingly, the CD56 dim NK-cell profile predicted time to HBV surface antigen (HBsAg) clearance from the blood, and distinct NK-cell profiles predicted early (NKp30, CD94, CD161) and late clearance (KIR3DL1, CD158a, perforin, NKp46). Finally, functional analysis demonstrated that early and late clearance tracked with elevated degranulation (CD107a) or IFNγ production, respectively, in response to ADCC-mediated activation. In conclusion, the cytolytic CD56dim NK-cell subset is selectively activated in acute HBV infection and displays distinct phenotypic and functional profiles associated with efficient and early control of HBV, implicating antibody-mediated cytolytic NK-cell responses in the early control and functional cure of HBV infection.

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Non-Invasive Treatment of Pediatric Neurological Disorders using MR-guided Focused Ultrasound - Part 1 Pediatric Skull Characterization and Re-Focusing

10.31225/osf.io/yt6qd ◽

2018 ◽

Author(s):

James Drake

Keyword(s):

Focused Ultrasound ◽

Pediatric Patients ◽

Current Treatment ◽

Acoustic Properties ◽

Invasive Treatment ◽

Non Invasive ◽

Treatment Techniques ◽

Early Results ◽

Intracerebral Hemorrhages ◽

Surrounding Areas

The concept of brain lesioning is well established in adult tremor and early results from MRgFUS trials have shown great efficiacy. In addition, work has been done to show that is possible to target and ablate tumors with transcranial systems. However, there is little to no work performed on neonatal and pediatric patients. Based on clinical presentation of IVH and epilepsy, there is a clear clinical need for non-invasive treatments as current treatment techniques have complications (eg. secondary intracerebral hemorrhages from tPA). With our initial data, neonatal and pediatric patients possess unique skull and brain properties that facilitate and simplify the transmission of focused ultrasound. The open fontanelle and thinner skulls potentially reduce the need for lower frequencies which opens up the possibility of using existing MRgFUS transducers to perform the treatment and reduce the upfront investments. Our project will characterize the acoustic properties of pediatric skulls over 3 frequencies, develop a refocusing algorithm based on the acoustic data, simulate the acoustic transmission through the skull to study the effects on the target and surrounding areas and validate the algorithm on a porcine model.

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Circulating Activated Immune Cells as a Potential Blood Biomarkers of Non-small Cell Lung Cancer Occurrence and Progression

10.21203/rs.3.rs-464238/v1 ◽

2021 ◽

Author(s):

Yingyi Wang ◽

Na Zhou ◽

Rui Zhu ◽

Xiaoyuan Li ◽

Zhao Sun ◽

...

Keyword(s):

T Cells ◽

Nk Cells ◽

Immune Cells ◽

Cd4 T Cells ◽

Small Cell Lung ◽

Early Screening ◽

Lymphocyte Ratio ◽

Non Invasive ◽

Hla Dr ◽

Nsclc Patients

Abstract Background: Non-small cell lung cancer (NSCLC) has improved greatly in recent years. However, non-invasive early screening for carcinogenesis and progression are unclearly. The aim of this study was to explore the predictive value of peripheral blood immune cells in untreated NSCLC patients. Methods: We retrospectively enrolled 305 untreated NSCLC patients and 132 healthy participators from February 2016 to August 2019. Immune cells levels were performed by flow cytometry and blood routine tests. Results: NSCLC patients had lower levels of T lymphocytes, NK cells, CD8+ T cells, naïve CD4+/ CD4+, naïve CD4+ T cells and higher levels of CD4+ T cells, memory CD4+/CD4+, memory CD4+ T cells, CD4+CD28+/CD4+, CD4+CD28+ T cells, CD8+CD28+/CD8+, CD8+HLA-DR+/CD8+, CD8+HLA-DR+ T cells, CD8+CD38+/CD8+, CD8+CD38+ T cells and CD4+/CD8+ than those in controls. Cancer progression were negatively associated with levels of B cells, CD4+ T cells, naïve CD4+/CD4+, naïve CD4+ T cells, CD4+CD28+ T cells, CD8+CD28+ T cells and positively associated with levels of NK cells, white blood cells (WBC), monocytes, neutrophils, eosinophils, basophils, monocytes to lymphocyte ratio (MLR), neutrophils to lymphocyte ratio (NLR), eosnophil to lymphocyte ratio (ELR), basophil to lymphocyte ratio (BLR), blood platelet to lymphocyte ratio (PLR) .Conclusions: Abnormal levels of NK cells, CD4+ T cells, naïve CD4+/CD4+, naïve CD4+ T cells, CD4+CD28+ T cells can be used as independently predictive biomarker for non-invasive early screening in NSCLC occurrence and progression.

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Efficacy of chronic ultrasound neurostimulation on behaviors and distributed brain metabolism in depressive-like mice

10.1101/813006 ◽

2019 ◽

Author(s):

Marc Legrand ◽

Laurent Galineau ◽

Anthony Novell ◽

Barbara Planchez ◽

Bruno Brizard ◽

...

Keyword(s):

Major Depression ◽

Therapeutic Potential ◽

Treatment Strategies ◽

Chronic Mild Stress ◽

Current Treatment ◽

Transcranial Ultrasound ◽

Anxiety And Depression ◽

Mild Stress ◽

Non Invasive ◽

Invasive Method

AbstractMajor depression is one of the main factors contributing to the Global Burden of Disease. Current treatment strategies (e.g., antidepressants and neurostimulation techniques) of major depression show some limitations including inaccuracy and invasiveness. Ultrasound neurostimulation (USNS) has been recently introduced as a physical non-invasive method for brain tissue stimulation and has gained increasing interest. In this study, we sought to evaluate the efficacy of transcranial USNS in an unpredictable chronic mild stress (UCMS) mouse model. The results show that transcranial USNS of the infralimbic cortex reduced anxiety-related behaviors as well as some, but not all, depression-related parameters. [18F]-FDG microPET imaging and brain metabolomic analyses showed that USNS triggered the activation of targeted brain region in addition to brain areas at a distance from the targeted zone, alleviating anxiety and depression-related behaviors induced by the UCMS regimen. Transcranial ultrasound neurostimulation show therapeutic potential in some aspects of major depression.

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Specific immunotherapy in patients with infectious -and-allergic rhinitis

Kazan medical journal ◽

10.17816/kazmj82713 ◽

1995 ◽

Vol 76 (1) ◽

pp. 36-37

Author(s):

F. A. Fattakhova

Keyword(s):

Allergic Rhinitis ◽

Immune System ◽

Cellular Immunity ◽

Specific Immunotherapy ◽

Clinical Results ◽

Immune Disorders ◽

Humoral And Cellular Immunity

The improvement and normalization of the characteristics of humoral and cellular immunity and nonspecific organism protection correspond to the good and excellent results of immunotherapy, whereas in unsatisfactory and satisfactory results the pathologic ships in immune system are conserved,, ov the insignificant positive dynamics of immunologic characteristics is observed. The presence ot immune disorders after the immunotherapy course by bacterial allergens is an indication for the following extension without regard to the clinical results obtained up to, the normalisation and improvehent of immunologic characteristics.

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Modern possibilities for the diagnosis of adenomyosis

Journal of obstetrics and women s diseases ◽

10.17816/jowd69173-80 ◽

2020 ◽

Vol 69 (1) ◽

pp. 73-80

Author(s):

Maria A. Shalina ◽

Maria I. Yarmolinskaya ◽

Elena I. Abashova

Keyword(s):

Review Article ◽

Non Invasive ◽

Immunological Factors

This review article presents modern data on the diagnosis and pathogenesis of adenomyosis, various classifications of the disease being highlighted. The role of genetic and immunological factors in the development of internal endometriosis is discussed. The results of domestic and foreign studies are presented, with the most informative non-invasive markers for the diagnosis of adenomyosis described.

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