Umeå University's logo

umu.sePublications
Change search
Refine search result
1 - 12 of 12
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Björk, Emma
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry. Division of Obstetrics and Gynecology/Örnsköldsvik Hospital, Örnsköldsvik, Sweden.
    Israelsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nagaev, Ivan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Endometriotic tissue-derived exosomes downregulate NKG2D-mediated cytotoxicity and promote apoptosis: mechanisms for survival of endometriotic tissue at ectopic sites2024Manuscript (preprint) (Other academic)
    Abstract [en]

    Endometriosis, affecting 10% of women, is defined as implantation, survival, and growth of endometriumlike/endometriotic tissue outside the uterine cavity, causing inflammation, infertility, pain andsusceptibility to ovarian cancer. Despite extensive studies, its etiology and pathogenesis are poorlyunderstood and largely unknown. The prevailing view is that the immune system of endometriosispatients fails to clear ectopically disseminated endometrium from retrograde menstruation. Exosomes aresmall extracellular vesicles that exhibit immunomodulatory properties. We studied the role ofendometriotic tissue-secreted exosomes in the pathophysiology of endometriosis. Two exosome-mediatedmechanisms known to impair the immune response were investigated: 1) downregulation of NKG2Dmediatedcytotoxicity and 2) FasL- and TRAIL-induced apoptosis of activated immune cells. We showedthat secreted endometriotic exosomes isolated from supernatants of short-term explant cultures carry theNKG2D ligands MICA/B and ULBP1-3; and the proapoptotic molecules FasL and TRAIL on theirsurface, i.e. signature molecules of exosome-mediated immune suppression. Acting as decoys, theseexosomes downregulate the NKG2D receptor, impair NKG2D-mediated cytotoxicity and induce apoptosisof activated PBMC and Jurkat cells through the FasL- and TRAIL pathway. The secreted endometrioticexosomes create an immunosuppressive gradient at the ectopic site, forming a “protective shield” aroundthe endometriotic lesions. This gradient guards the endometriotic lesions against clearance by a cytotoxicattack and creates immunologic privilege by induction of apoptosis in activated immune cells. Takentogether, our results provide a plausible, exosome-based mechanistic explanation for the immunedysfunction and the compromised immune surveillance in endometriosis and contribute with novelinsights into the pathogenesis of this enigmatic disease.

  • 2.
    Björk, Emma
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry. Division of Obstetrics and Gynecology/Örnsköldsvik Hospital, Örnsköldsvik, Sweden.
    Israelsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Enhanced CD56 expression and increased numbers of CD56+bright cells in the peripheral blood of untreated endometriosis patientsManuscript (preprint) (Other academic)
    Abstract [en]

    Problem: Endometriosis is characterized by ectopic implantation of endometrial-like tissue and impaired immuneresponses such as the cytotoxic function of NK cells. NK cells can be divided into two subpopulations where theCD56+bright cells produce more cytokines and have low natural cytotoxicity compared to CD56+dim cells. Themajority (>90%) of circulating NK cells are CD56+dim whereas very few (0-10 %) are CD56+bright.

    Method of Study: Using flow cytometry, NK cell subpopulations were analyzed in peripheral blood from 21individuals with endometriosis and 12 healthy controls. Furthermore, the NKG2D receptor expression on PBMCswas analyzed in untreated and treated endometriosis patients and controls.

    Results: We found an increased level of CD56+bright cells in 8 of 21 endometriosis patients. After surgery andhormonal treatment, the levels were normalized to that of controls. In a new cohort, the NKG2D receptorexpression on PBMCs was analyzed, with a lower expression in untreated patients compared to controls andpatients treated by surgery and hormones.

    Conclusions: Our findings of a dominant CD56+bright NK cell subpopulation in peripheral blood, anddownregulated levels of the NKG2D receptor on PBMCs, may explain the impaired cytotoxic immune functioncausing the persistence of ectopic endometrium in untreated endometriosis patients.

  • 3.
    Gideonsson, Ida
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Center of Obstetrics and Gynecology, Umeå University Hospital, Umeå, Sweden.
    Israelsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Strandberg, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Long-term follow-up of tamoxifen treatment and the use of imaging in psammocarcinoma: a case report, review of the literature and discussion of diagnostic and therapeutic challenges2023In: Current Oncology, ISSN 1198-0052, E-ISSN 1718-7729, Vol. 30, no 12, p. 10260-10271Article in journal (Refereed)
    Abstract [en]

    Psammocarcinoma (PsC) represents a rare form of low-grade serous tumor of the ovary or peritoneum. Although ovarian cancer generally has a poor prognosis in its late stages, PsC seems to have a more indolent course. We present a patient with a history of unspecific abdominal pain for more than a year, with sudden acute onset of severe inguinal pain. On admission to the hospital, a computed tomography (CT) revealed a pelvic mass of suspected ovarian origin. Radical surgery was attempted but not achieved due to widespread tumor growth. Histopathological evaluation revealed estrogen receptor-positive stage III PsC. Tamoxifen treatment was thus initiated, still maintaining stable disease 10 years later. The patient has undergone extensive radiological work-up, including CT, chest X-ray, 18F-fluoro-deoxy-glucose positron emission tomography (PET)/CT, 99mTc- hydroxymethylene diphosphonate (HDP) bone scintigraphy, 18F-fluoro-thymidine (FLT) PET/CT, Tc-99m depreotide scintigraphy and magnetic resonance imaging. In conclusion, we demonstrate that PsC has characteristic radiological features and different imaging modalities can be suitable in different clinical situations. In contrast to most other ovarian cancers, PsC does not always warrant adjuvant chemotherapy, even in advanced stages. This emphasizes the need for a deeper knowledge of the biological behavior of this rare tumor, to select the optimal treatment strategy.

    Download full text (pdf)
    fulltext
  • 4.
    Green, Caroline
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Professional Development.
    Mettävainio, Martin Isaksson
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Kjellman, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Professional Development.
    Ramqvist, Torbjörn
    Department of Oncology‑Pathology, Karolinska Institute, Stockholm, Sweden.
    Dalianis, Tina
    Department of Oncology‑Pathology, Karolinska Institute, Stockholm, Sweden.
    Israelsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindquist, David
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Professional Development.
    Combined treatment with radiotherapy, chemotherapy and avelumab results in regression of metastatic Merkel cell carcinoma and improvement of associated Lambert‑Eaton myasthenic syndrome: a case report2022In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 24, no 5, article id 393Article in journal (Refereed)
    Abstract [en]

    Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy arising from mecha‑ noreceptors in the basal epidermis. Due to a pronounced risk of spread and a high propensity for recurrence after treatment, immediate treatment is of utmost importance. Lambert‑Eaton myasthenic syndrome (LEMS) is a paraneoplastic phenom‑ enon affecting the muscles with autoimmune pathophysiology, and >50% of known cases are associated with an underlying malignancy. In the present report, the case of a 67‑year‑old man presenting with progressive proximal muscle weakness, auto‑ nomic dysfunction and involuntary weight loss is described. Symptoms and detection of voltage‑gated calcium channel antibodies were consistent with LEMS. Distant metastases were found in the inguinal and iliac lymph nodes, and these were immunohistochemically confirmed to be of epithelial and neuroendocrine origin, consistent with MCC. Local radio‑ therapy and chemotherapy improved the symptoms; however, a change of treatment was required due to the side effects of the chemotherapy. Avelumab, an immune checkpoint inhibitor, was therefore introduced, and within a year the patient did not only experience tumor remission but also exhibited marked improvements in muscle strength and mobility. At present, 2 years later, the MCC is still in remission. To the best of our knowledge, the present report is the first to describe MCC with associated LEMS, which was successfully treated with avelumab after previous radiotherapy and chemotherapy, with both improved functional motor recovery and tumor reduc‑ tion. In conclusion, the present case report demonstrated that the present treatment strategy is a potential treatment option and could thus be considered in similar cases.

    Download full text (pdf)
    fulltext
  • 5.
    Israelsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Mechanisms for immune escape in epithelial ovarian cancer2021Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Tumors develop mechanisms to subvert the immune system, constituting immune escape. Epithelial ovarian cancer (EOC), the deadliest of all gynecological malignancies, uses a variety of mechanisms to undermine immune surveillance, aiding its establishment and metastatic spreading. Despite progress in oncoimmunology, a lot remains unknown about the cancer-immune system interplay. The aim of this thesis was to study tumor-mediated mechanisms for immune escape in EOC patients, focusing on the role of cytokines and EOC- derived exosomes. 

    Cytokines are key molecules regulating immune effector functions in health and disease. We used real-time RT-qPCR and a set of primers and probes for 12 cytokines, discriminating between different immune responses and compared the cytokine mRNA expression profiles locally in the TME and systemically in peripheral blood immune cells of EOC patients, to women with benign ovarian conditions and women with normal ovaries. The cytokine mRNA expression was in general most prominent in EOC patients, confirming the immunogenicity of EOC. We found significant dominance of inflammatory and immunosuppressive/ regulatory cytokines, known to promote tumor progression by priming and activating T regulatory cell-mediated immune suppression. In contrast, IFN-γ, crucially important for evoking a cytotoxic anti-tumor response, was not upregulated. Instead, a systemic increase of IL-4 prevailed, deviating the immune defense towards humoral immunity. With regard to our cytokine study, we performed comparative analyses of cytokine mRNA versus protein expression in the EOC cell lines OVCAR-3 and SKOV-3. We found that cytokine mRNA signals were universally detected, and in some instances translated into proteins, but the protein expression levels depended on the material analyzed and the method used. Due to the high sensitivity of real-time RT-qPCR, we suggest that cytokine mRNA expression profiles can be used for some instances, such as in studies of mechanistic pathways and in comparisons between patient groups, but cannot replace expression at the protein level. 

    Exosomes are nanometer-sized vesicles of endosomal origin, released by virtually all cells, participating in normal and pathological processes. Like many tumors, EOC is a great exosome producer. We isolated exosomes from EOC ascitic fluid and supernatant from tumor explant cultures to study their effect on the NK cell receptors NKG2D and DNAM-1, involved in tumor killing. We found that EOC exosomes constitutively expressed NKG2D ligands on their surface while DNAM-1 ligand expression was rare and not associated with the exosomal membrane. Consistently, the major cytotoxic pathway of NKG2D-mediated killing was dysregulated by EOC exosomes while the accessory DNAM-1- mediated pathway remained unchanged. Our results provide a mechanistic explanation to the previously made observation that in EOC patients, tumor killing is only dependent on the accessory DNAM-1 pathway. Following these iii iv results, we studied NKG2D-mediated cytotoxicity in vivo in EOC patients before and after surgery. We found that the serum exosomes isolated from EOC patients were able to downregulate the NKG2D receptor and suppress NKG2D-mediated cytotoxicity in NK cells from healthy donors, in a similar way as exosomes from EOC ascites. We also found that surgery of the primary EOC tumor has a beneficial effect on the patients’ anti-tumor cytotoxic immune response. One mechanistic explanation could be a decrease in circulating NKG2D ligand- expressing exosomes, thus improving the cytotoxic NK cell function. 

    In conclusion, our results contribute to the understanding of the mechanisms responsible for tumor immune escape in general, and in EOC patients in particular, and might be useful in developing novel antitumor therapies. Our studies highlight the prevailing immunosuppression in the local TME and the immunosuppressive role of EOC exosomes. Furthermore, they support the notion that cancer surgery is also a way of removing exosome-producing cells and reducing the serum concentration of immunosuppressive exosomes, thus boosting the patients’ cytotoxic anti-tumor response. 

    Download full text (pdf)
    fulltext
    Download (pdf)
    spikblad
    Download (jpg)
    presentationsbild
  • 6.
    Israelsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björk, Emma
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaev, Ivan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    NKG2D-mediated cytotoxicity improves after primary surgery for high-grade serous ovarian cancer2023In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 89, no 1, article id e13647Article in journal (Refereed)
    Abstract [en]

    Problem: Tumors compromise the patients’ immune system to promote their own survival. We have previously reported that HGSC exosomes play a central role, downregulating NKG2D cytotoxicity. Primary surgery's effect on tumor exosomes and NKG2D cytotoxicity in HGSC patients has not been studied before. The overall objective of this study was to explore the effect of surgery on the exosome-induced impairment of NKG2D cytotoxicity in HGSC.

    Method of study: Paired pre- and post-operative blood samples were subjected to cell and exosome analyses regarding the NKG2D receptor and ligands, and NKG2D-mediated cytotoxicity. Lymphocytes were phenotyped by immunoflow cytometry. Exosomes, isolated by ultracentrifugation, and characterized by nanoparticle tracking analysis, transmission and immune electron microscopy and western blot were used in functional cytotoxic experiments. HGSC explant culture-derived exosomes, previously studied by us, were used for comparison.

    Results: HGSC exosomes from patients’ sera downregulated NKG2D-mediated cytotoxicity in NK cells of healthy donors. In a subgroup of subjects, NKG2D expression on CTLs and NK cells was upregulated after surgery, correlating to a decrease in the concentration of exosomes in postoperative sera. An overall significantly improved NKG2D-mediated cytotoxic response of the HGSC patients’ own NK cells in postoperative compared to preoperative samples was noted.

    Conclusions: Surgical removal of the primary tumor has a beneficial effect, relieving the exosome-mediated suppression of NKG2D cytotoxicity in HGSC patients, thus boostering their ability to combat cancer.

    Download full text (pdf)
    fulltext
  • 7.
    Israelsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Björk, Emma
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Nagaev, Ivan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    The influence of surgery on circulating ovarian cancer exosomes and the NKG2D‐mediated cytotoxicityManuscript (preprint) (Other academic)
  • 8.
    Israelsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Dehlin, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaev, Ivan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Cytokine mRNA and protein expression by cell cultures of epithelial ovarian cancer: Methodological considerations on the choice of analytical method for cytokine analyses2020In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 84, no 1, article id e13249Article in journal (Refereed)
    Abstract [en]

    Problem: To get a comprehensive picture of cytokine expression in health and disease is difficult, cytokines are transiently and locally expressed, and protein analyses are burdened by biological modifications, technical issues, and sensitivity to handling of samples. Thus, alternative methods, based on molecular techniques for cytokine mRNA analyses, are often used. We compared cytokine mRNA and protein expression to evaluate whether cytokine mRNA profiles can be used instead of protein analyses.

    Method of study: In kinetic experiments, cytokine mRNA and protein expression of IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta/LTA were studied using real-time RT-qPCR and Luminex(R) microarrays in the ovarian cancer cell lines OVCAR-3, SKOV-3 and the T-cell line Jurkat, after activation of transcription by thermal stress. In addition, we analyzed IL-6 and IL-8 mRNA and protein in a small number of ovarian cancer patients.

    Results: Ovarian cancer cells can express cytokines on both mRNA and protein level, with 1-4 hours' time delay between the mRNA and protein peak and a negative Spearman correlation. The mRNA and protein expression in patient samples was poorly correlated, reflecting previous studies.

    Conclusion: Cytokine mRNA and protein expression levels show diverging results, depending on the material analyzed and the method used. Considering the high sensitivity and reproducibility of real-time RT-qPCR, we suggest that cytokine mRNA profiles could be used as a proxy for protein expression for some specific purposes, such as comparisons between different patient groups, and in defining mechanistic pathways involved in the pathogenesis of cancer and other pathological conditions.

    Download full text (pdf)
    fulltext
  • 9.
    Israelsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Labani-Motlagh, Alireza
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaev, Ivan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Dehlin, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary2019In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 29, p. A138-A138Article in journal (Other academic)
    Abstract [en]

    Introduction/Background Tumor establishment, metastatic spreading and poor survival in ovarian cancer is strongly associated with progressive derangement of the patient‘s immune system. Accumulating evidence suggests that immune impairment is influenced by the production and presence of cytokines in the tumor microenvironment.

    Methodology Cytokine mRNA profiles in tumor tissue and peripheral blood mononuclear cells (PBMC) were analyzed in patients with high grade serous carcinoma (HGSC) of the ovary and compared it to patients with benign ovarian conditions and controls with normal ovaries. Cytokine assessment was done by real-time quantitative RT-PCR and specific primers and probes for 12 cytokines-IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, TNF-β/LTA, TGF-β1, and GM-CSF chosen to distinguish between cytotoxic Th1, humoral Th2, regulatory Th3/Tr1 and inflammatory responses.

    Results The cytokine mRNA response in the HGSC patients was significantly up regulated compared to patients with benign ovarian conditions and normal ovary controls confirming the immunogenicity of HGSC and implying immune recognition and reaction locally in the tumor microenvironment and systemically in the peripheral blood.There was an up-regulation of inflammatory and inhibitory cytokine mRNA promoting tumor progression, T-regulatory cell priming and T-regulatory cell-mediated immune suppression. In contrast, there was an inability to mount the crucially important IFN gamma response needed for upregulation of the cytotoxic anti-tumor response in the local microenvironment. In addition, systemic IL-4- mediated Th2 response prevailed in the peripheral blood deviating the systemic defense towards humoral immunity.

    Conclusion Taken together, these results suggest local and systemic cytokine cooperation promoting tumor survival, progression and immune escape. Our study confirms and extends previous investigations and contributes to the evaluation of potential cytokine candidates for diagnostic cytokine mRNA profiles and for future therapeutic interventions based on cytokine inhibition.

  • 10.
    Israelsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Labani-Motlagh, Alireza
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaev, Ivan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Dehlin, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary2017In: Journal of Cancer Science & Therapy, ISSN 1948-5956, Vol. 9, no 5, p. 422-429Article in journal (Refereed)
    Abstract [en]

    Objective: Tumor establishment, metastatic spreading and poor survival in ovarian cancer is strongly associated with progressive derangement of the patient’s immune system. Accumulating evidence suggests that immune impairment is influenced by the production and presence of cytokines in the tumor microenvironment. Methods: Cytokine mRNA profiles in tumor tissue and peripheral blood mononuclear cells (PBMC) were analyzed in patients with high grade serous carcinoma (HGSC) of the ovary and compared it to patients with benign ovarian conditions and controls with normal ovaries. Cytokine assessment was done by real-time quantitative RT-PCR and specific primers and probes for 12 cytokines-IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, TNF-β/LTA, TGF-β1, and GM-CSF chosen to distinguish between cytotoxic Th1, humoral Th2, regulatory Th3/Tr1 and inflammatory responses. Results: The cytokine mRNA response in the HGSC patients was significantly up regulated compared to patients with benign ovarian conditions and normal ovary controls confirming the immunogenicity of HGSC and implying immune recognition and reaction locally in the tumor microenvironment and systemically in the peripheral blood.There was an up-regulation of inflammatory and inhibitory cytokine mRNA promoting tumor progression, T-regulatory cell priming and T-regulatory cell-mediated immune suppression. In contrast, there was an inability to mount the crucially important IFN gamma response needed for upregulation of the cytotoxic anti-tumor response in the local microenvironment. In addition, systemic IL-4- mediated Th2 response prevailed in the peripheral blood deviating the systemic defense towards humoral immunity. Conclusions: Taken together, these results suggest local and systemic cytokine cooperation promoting tumor survival, progression and immune escape. Our study confirms and extends previous investigations and contributes to the evaluation of potential cytokine candidates for diagnostic cytokine mRNA profiles and for future therapeutic interventions based on cytokine inhibition.

    Download full text (pdf)
    fulltext
  • 11.
    Israelsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Oda, Husam
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Öfverman, Charlotte
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Stefansson, Kristina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lindquist, David
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    High LMO-7 expression is a positive prognostic factor in oropharyngeal squamous cell carcinomaManuscript (preprint) (Other academic)
  • 12.
    Labani-Motlagh, Alireza
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Israelsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nagaev, Ivan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Dehlin, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Baranov, Vladimir
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity2016In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 37, no 4, p. 5455-5466Article in journal (Refereed)
    Abstract [en]

    Cancers constitutively produce and secrete into the blood and other biofluids 30-150 nm-sized endosomal vehicles called exosomes. Cancer-derived exosomes exhibit powerful influence on a variety of biological mechanisms to the benefit of the tumors that produce them. We studied the immunosuppressive ability of epithelial ovarian cancer (EOC) exosomes on two cytotoxic pathways of importance for anticancer immunity-the NKG2D receptor-ligand pathway and the DNAM-1-PVR/nectin-2 pathway. Using exosomes, isolated from EOC tumor explant and EOC cell-line culture supernatants, and ascitic fluid from EOC patients, we studied the expression of NKG2D and DNAM-1 ligands on EOC exosomes and their ability to downregulate the cognate receptors. Our results show that EOC exosomes differentially and constitutively express NKG2D ligands from both MICA/B and ULBP families on their surface, while DNAM-1 ligands are more seldom expressed and not associated with the exosomal membrane surface. Consequently, the NKG2D ligand-bearing EOC exosomes significantly downregulated the NKG2D receptor expression on peripheral blood mononuclear cells (PBMC) while the DNAM-1 receptor was unaffected. The downregulation of NKG2D receptor expression was coupled to inhibition of NKG2D receptor-ligand-mediated degranulation and cytotoxicity measured in vitro with OVCAR-3 and K562 cells as targets. The EOC exosomes acted as a decoy impairing the NKG2D mediated cytotoxicity while the DNAM-1 receptor-ligand system remained unchanged. Taken together, our results support and explain the mechanism behind the recently reported finding that in EOC, NK-cell recognition and killing of tumor cells was mainly dependent on DNAM-1 signaling while the contribution of the NKG2D receptor-ligand pathway was complementary and uncertain.

1 - 12 of 12
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf