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Mincheva-Nilsson, Lucia
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Publications (10 of 48) Show all publications
Vinnars, M.-T., Björk, E., Nagaev, I., Ottander, U., Bremme, K., Holmlund, U., . . . Mincheva-Nilsson, L. (2018). Enhanced Th1 and inflammatory mRNA responses upregulate NK cell cytotoxicity and NKG2D ligand expression in human pre-eclamptic placenta and target it for NK cell attack. American Journal of Reproductive Immunology, 80(1), Article ID e12969.
Open this publication in new window or tab >>Enhanced Th1 and inflammatory mRNA responses upregulate NK cell cytotoxicity and NKG2D ligand expression in human pre-eclamptic placenta and target it for NK cell attack
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2018 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 80, no 1, article id e12969Article in journal (Refereed) Published
Abstract [en]

Problem: Pre-eclampsia (PE), a severe human pregnancy disorder, is associated with exaggerated systemic inflammation, enhanced cytokine production, and increased shedding of microvesicles leading to endothelial dysfunction, coagulopathy, and extensive placenta destruction. The cause of PE is still unclear. Evidence suggests that its origin lies in the placenta and that the maternal immune system is involved. A shift in cytokine production in PE pregnancy promotes NK cell activation, suggested to be important in PE pathogenesis. In line with this suggestion, we studied NK cell cytotoxicity in peripheral blood of PE patients and controls and the mRNA expression of cytokines and of the NKG2D receptor and its ligands MICA/B and ULBP1-3 in PE- and normal placenta.

Method of study: The cytotoxic capacity of peripheral blood NK cells was analyzed using K562 target cells. The cytokine mRNA profiles and the mRNA expression of the NKG2D receptor and its ligands MICA/B and ULBP 1-3 in PE placenta were assessed and compared to those in normal placenta using real-time quantitative RT-PCR.

Results: The cytotoxicity of peripheral blood NK cells was upregulated in PE cases. Further, we found an enhanced inflammatory cytokine mRNA response combined with a dysregulated regulatory response and a significant mRNA overexpression of NKG2D receptor and its ligands MICA/B and ULBP in PE placenta.

Conclusion: The destruction of chorionic villi observed in PE placenta might be conveyed by an enhanced local cytotoxic response through the NKG2D receptor-ligand pathway, which in turn might be promoted by an intense inflammatory response not counteracted by regulatory cytokine responses.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
cytokines, inflammation, natural killer cells, NKG2D receptor-ligand system, pre-eclampsia, Treg
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-150750 (URN)10.1111/aji.12969 (DOI)000436401600013 ()29741244 (PubMedID)2-s2.0-85046661409 (Scopus ID)
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved
Israelsson, P., Labani-Motlagh, A., Nagaev, I., Dehlin, E., Nagaeva, O., Lundin, E., . . . Mincheva-Nilsson, L. (2017). Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary. Journal of Cancer Science & Therapy, 9(5), 422-429
Open this publication in new window or tab >>Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary
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2017 (English)In: Journal of Cancer Science & Therapy, ISSN 1948-5956, Vol. 9, no 5, p. 422-429Article in journal (Refereed) Published
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.

Keywords
Cytokines, High-grade serous ovarian carcinoma (HGSC), EOC, Tumor microenvironment, Tumor inflammation, Immune suppression
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-138256 (URN)10.4172/1948-5956.1000453 (DOI)
Available from: 2017-08-15 Created: 2017-08-15 Last updated: 2018-06-09Bibliographically approved
Holm, A., Nagaeva, O., Nagaev, I., Loizou, C., Laurell, G., Mincheva-Nilsson, L., . . . Olofsson, K. (2017). Lymphocyte profile and cytokine mRNA expression in peripheral blood mononuclear cells of patients with recurrent respiratory papillomatosis suggest dysregulated cytokine mRNA response and impaired cytotoxic capacity. Immunity, Inflammation and Disease, 5(4), 541-550
Open this publication in new window or tab >>Lymphocyte profile and cytokine mRNA expression in peripheral blood mononuclear cells of patients with recurrent respiratory papillomatosis suggest dysregulated cytokine mRNA response and impaired cytotoxic capacity
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2017 (English)In: Immunity, Inflammation and Disease, E-ISSN 2050-4527, Vol. 5, no 4, p. 541-550Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is a relatively rare, chronic disease caused by Human Papilloma Virus (HPV) 6 and 11, and characterized by wart-like lesions in the airway affecting voice and respiratory function. The majority of HPV infections are asymptomatic and resolve spontaneously, however, some individuals are afflicted with persistent HPV infections. Failure to eliminate HPV 6 and 11 due to a defect immune responsiveness to these specific genotypes is proposed to play a major role in the development of RRP.

METHODS: We performed a phenotypic characterization of peripheral blood mononuclear cells (PBMC) collected from 16 RRP patients and 12 age-matched healthy controls, using immunoflow cytometry, and monoclonal antibodies against differentiation and activation markers. The cytokine mRNA profile of monocytes, T helper-, T cytotoxic-, and NK cells was assessed using RT-qPCR cytokine analysis, differentiating between Th1-, Th2-, Th3/regulatory-, and inflammatory immune responses.

RESULTS: We found a dominance of cytotoxic T cells, activated NK cells, and high numbers of stressed MIC A/B expressing lymphocytes. There was an overall suppression of cytokine mRNA production and an aberrant cytokine mRNA profile in the activated NK cells.

CONCLUSION: These findings demonstrate an immune dysregulation with inverted CD4(+) /CD8(+) ratio and aberrant cytokine mRNA production in RRP patients, compared to healthy controls.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2017
Keywords
Human, T Cells, natural killer T cells, viral/retroviral
National Category
Immunology Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-142017 (URN)10.1002/iid3.188 (DOI)000424098900015 ()28805308 (PubMedID)
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2019-04-29Bibliographically approved
Andersen, M., Nagaev, I., Meyer, M. K., Nagaeva, O., Wikberg, J., Mincheva-Nilsson, L. & Andersen, G. N. (2017). Melanocortin 2, 3 and 4 Receptor Gene Expressions are Downregulated in CD8(+) T Cytotoxic Lymphocytes and CD19(+) B Lymphocytes in Rheumatoid Arthritis Responding to TNF- Inhibition. Scandinavian Journal of Immunology, 86(1), 31-39
Open this publication in new window or tab >>Melanocortin 2, 3 and 4 Receptor Gene Expressions are Downregulated in CD8(+) T Cytotoxic Lymphocytes and CD19(+) B Lymphocytes in Rheumatoid Arthritis Responding to TNF- Inhibition
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 1, p. 31-39Article in journal (Refereed) Published
Abstract [en]

Melanocortin signalling in leucocyte subsets elicits anti-inflammatory and immune tolerance inducing effects in animal experimental inflammation. In man, however, the effects of melanocortin signalling in inflammatory conditions have scarcely been examined. We explored the differential reactions of melanocortin 1-5 receptors (MC1-5R) gene expressions in pathogenetic leucocyte subsets in rheumatoid arthritis (RA) to treatment with TNF- inhibitor adalimumab. Seven patients with active RA donated blood at start and at 3-month treatment. CD4(+) T helper (h) lymphocytes (ly), CD8(+) T cytotoxic (c) ly, CD19(+) B ly and CD14(+) monocytes were isolated, using immunomagnetic beads, total RNA extracted and reverse transcription quantitative polymerase chain reaction (RT-qPCR) performed. Fold changes in MC1-5R, Th1-, inflammatory- and regulatory cytokine gene expressions were assessed for correlation. Six patients responded to adalimumab treatment, while one patient was non-responder. In all lymphocyte subtypes, MC1-5R gene expressions decreased in responders and increased in the non-responder. In responders, decrease in MC2R, MC3R and MC4R gene expressions in CD8(+) Tc and CD19(+) B ly was significant. Fold change in MC1-5R and IFN gene expressions correlated significantly in CD8(+) Tc ly, while fold change in MC1R, MC3R and MC5R and IL-1 gene expressions correlated significantly in CD4(+) Th ly. Our results show regulation of MC2R, MC3R and MC4R gene expressions in CD8(+) Tc ly and CD19(+) B ly. The correlations between fold change in different MCRs and disease driving cytokine gene expressions in CD8(+) Tc ly and CD4(+) Th ly point at a central immune modulating function of the melanocortin system in RA.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-137617 (URN)10.1111/sji.12555 (DOI)000403722100004 ()28426141 (PubMedID)
Available from: 2017-07-10 Created: 2017-07-10 Last updated: 2018-06-09Bibliographically approved
Wikström-Frisén, L., Larsson, P., Mincheva Nilsson, L. & Henriksson-Larsén, K. (2017). Mood and oxytocin blood levels in physically active women with and without oral contraceptive use in relation to seasonal daylight variation. International Journal of Sports and Exercise Medicine, 3(3), Article ID 058.
Open this publication in new window or tab >>Mood and oxytocin blood levels in physically active women with and without oral contraceptive use in relation to seasonal daylight variation
2017 (English)In: International Journal of Sports and Exercise Medicine, ISSN 2469-5718, Vol. 3, no 3, article id 058Article in journal (Refereed) Published
Abstract [en]

Background

The aim is to provide normative data on oxytocin, and its seasonality in users and non-users of Oral Contraceptives (OC) in physically active women. Further, to elucidate the relationship between Oxytocin and Profile of Mood States (POMS) for further research to see if Oxytocin can be used as an additional diagnostic marker to detect overreaching/overtraining syndrome or other stress disorders.

Methods

Forty-eight women (18-35 years old), 19 with and 29 without OC use, physically active at least 3 times a week at > 13 on the Borg RPE scale. Thirty-three subjects completed the study, 15 with and 18 without OC use. The number of hours from sunrise to sunset averaged 10 h during the autumn, 6 h during the winter, and 15 h during the spring. Once a month, blood samples were taken, weight and the day of menstrual cycle was documented, the POMS questionnaire was filled out as well as a personal daily logbook recording exercise type, duration, and intensity. To evaluate seasonal variations in Oxytocin and Global POMS, repeated measures analysis of variance was used.

Results

A significant seasonal variation in Oxytocin levels within the groups with and without OC respectively and significant differences in Oxytocin levels between the groups at diverse seasons were found. No significant difference in seasonal variation of Global POMS within the groups and no significant differences in levels of Global POMS between the groups with and without OC were seen. Furthermore, no clear relationship between Oxytocin, Global POMS scores, and hours of daylight respectively were detected.

Conclusions

Due to seasonality, impact of OC use on oxytocin levels, methodological considerations, and no convincing relationship to Global POMS, oxytocin is not suggested to be an optimal, diagnostic marker alone or in combination with others to detect overreaching and overtraining syndrome in physically active women.

Keywords
Oxytocin, Profile of Mood State, oral contraceptive use, females, hormone, seasonal variation, daylight
National Category
Sport and Fitness Sciences
Research subject
Physiology
Identifiers
urn:nbn:se:umu:diva-124822 (URN)10.23937/2469-5718/1510058 (DOI)
Available from: 2016-08-26 Created: 2016-08-26 Last updated: 2018-06-07Bibliographically approved
Labani-Motlagh, A., Israelsson, P., Ottander, U., Lundin, E., Nagaev, I., Nagaeva, O., . . . Mincheva-Nilsson, L. (2016). Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity. Tumor Biology, 37(4), 5455-5466
Open this publication in new window or tab >>Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity
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2016 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 37, no 4, p. 5455-5466Article in journal (Refereed) Published
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.

Keywords
Epithelial ovarian cancer/EOC, Tumor, Exosomes, NKG2D, DNAM-1/CD266, Cytotoxicity, MICA/B, ULBP, PVR, Nectin-2
National Category
Cancer and Oncology Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-118529 (URN)10.1007/s13277-015-4313-2 (DOI)000374904500128 ()26563374 (PubMedID)
Available from: 2016-03-22 Created: 2016-03-22 Last updated: 2018-06-07Bibliographically approved
Winberg, A., Nagaeva, O., Nagaev, I., Lundell, C., Arencibia, I., Mincheva Nilsson, L., . . . West, C. (2016). Dynamics of cytokine mRNA expression and fecal biomarkers in school-children undergoing a double-blind placebo-controlled food challenge series. Cytokine, 88, 259-266
Open this publication in new window or tab >>Dynamics of cytokine mRNA expression and fecal biomarkers in school-children undergoing a double-blind placebo-controlled food challenge series
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2016 (English)In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 88, p. 259-266Article in journal (Refereed) Published
Abstract [en]

Background: There is need for prognostic markers for symptomatic food allergy since current diagnostic methods are insufficient and/or time and labor consuming. Objective: To estimate the cytokine mRNA profiles in peripheral blood mononuclear cells (PBMC) before and after a double-blind placebo-controlled food challenge series in schoolchildren with suspected allergy to milk, egg or cod and in healthy controls. Analyses of fecal inflammatory biomarkers before and after the challenge were included. Methods: Twelve-year-old children from a population-based cohort reporting complete avoidance of milk, egg, cod or wheat due to perceived hypersensitivity were clinically examined and those with suspected food allergy were evaluated with a 3-session double-blind placebo-controlled food challenge (n = 18). Seven healthy controls participated in a double-blind challenge with egg. Before and after the challenge series, the cytokine mRNA expression was quantified for 13 cytokines discriminating between humoral Th2-, cytotoxic Thl-, regulatory Th3/Tr1- and inflammatory responses. Fecal calprotectin and eosinophil-derived neurotoxin (EDN) were also analyzed in children with suspected food allergy before and after the challenge series. Results: Pre challenge, children with suspected food allergy had higher IL-13 and TNF-alpha expression and lower IFN-gamma and IL-15 expression compared to healthy controls (all p < 0.05). Children with challenge proven food allergy had increased IL13 and IL-10 expression compared to the levels seen in negative challenges (p < 0.05). Post challenge, IL-1 beta and IL-6 mRNA levels were elevated in the food allergic children compared to controls (p < 0.05). Fecal calprotectin and EDN levels were higher in challenge-proven food allergy compared to a negative challenge although not statistically significantly. Conclusion & clinical relevance: Increased baseline mRNA levels of the Th2-related cytokine IL-13 and the regulatory cytokine IL-10 predicted a positive food challenge outcome. These cytokines in combination with fecal calprotectin and EDN might serve as future prognostic markers for symptomatic, IgEmediated food allergy but need further validation in a larger patient cohort.

Keywords
cytokines, fecal biomarkers, food allergy, children, IL-10, IL-13, tolerance
National Category
Pediatrics Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-114048 (URN)10.1016/j.cyto.2016.09.014 (DOI)000386862100033 ()27697703 (PubMedID)
Note

Originally published in thesis in manuscript form.

Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2018-06-07Bibliographically approved
Wikström-Frisén, L., Nordström, A., Mincheva-Nilsson, L. & Larsén, K. (2016). Impact of Season and Oral Contraceptive use on Cortisol Levelsin Physically Active Women. Journal of Exercise, Sports & Orthopedics, 3(2)
Open this publication in new window or tab >>Impact of Season and Oral Contraceptive use on Cortisol Levelsin Physically Active Women
2016 (English)In: Journal of Exercise, Sports & Orthopedics, ISSN 2374-6904, Vol. 3, no 2Article in journal (Refereed) Published
Abstract [en]

When athletes optimize their physical performance, an imbalance could occur between the strain of training, time for recovery and the athlete’s individual tolerance of stress that could lead to overreaching and overtraining syndrome. Cortisol has been suggested to be a biological, diagnostic marker to detect overreaching and overtraining syndrome, since it is thought to indicate stress. This study aimed to provide normative data on cortisol levels, hence investigate seasonality and impact of oral contraceptive use to elucidate if cortisol could be used as a diagnostic marker to detect overreaching and overtraining syndrome in female athletes. The women, divided in two groups, oral contraceptive users (n = 15) and non-users (n = 18), were followed over a nine-month period with monthly blood sampling for cortisol testing and a Profile of Mood State questionnaire (POMS) as a subjective measure of overreaching and overtraining syndrome.Findings indicated seasonal variations in cortisol levels, with different pattern in oral contraceptive users to non-users and moreover, higher cortisol levels in users to nonusers irrespective of season. No differences in seasonal variation in Global POMS score within the groups and no differences in Global POMS score between the groups were detected. Due to seasonality, impact of oral contraceptive use on cortisol levels, methodological considerations and standardization, as well as due to no convincing relationship to Global POMS score, cortisol is not suggested to be an optimal biological, diagnostic marker to detect overreaching and overtraining syndrome in physically active women.

Keywords
hormones, overreaching, overtraining syndrome, female athletes, Profile of Mood State
National Category
Sport and Fitness Sciences
Research subject
Physiology
Identifiers
urn:nbn:se:umu:diva-124841 (URN)
Available from: 2016-08-26 Created: 2016-08-26 Last updated: 2018-06-07Bibliographically approved
Andersen, M., Olesen, M. K., Nagaev, I., Nagaeva, O., Wikberg, J., Mincheva-Nilsson, L. & Andersen, G. N. (2014). Adalimumab (Humira (R)) normalizes melanocortin receptor subtype 2, 3, and 4 expression in CD8+, CD14+, and CD19+leucocyte subsets in rheumatoid arthritis. Scandinavian Journal of Rheumatology, 43(Suppl. 127), 25-26 Meeting Abstr. PP119
Open this publication in new window or tab >>Adalimumab (Humira (R)) normalizes melanocortin receptor subtype 2, 3, and 4 expression in CD8+, CD14+, and CD19+leucocyte subsets in rheumatoid arthritis
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2014 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, no Suppl. 127, p. 25-26 Meeting Abstr. PP119Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Informa Healthcare, 2014
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-94906 (URN)000341757300038 ()
Available from: 2014-10-28 Created: 2014-10-20 Last updated: 2018-06-07Bibliographically approved
Mincheva-Nilsson, L. & Baranov, V. (2014). Cancer exosomes and NKG2D receptor-ligand interactions: impairing NKG2D-mediated cytotoxicity and anti-tumour immune surveillance. Seminars in Cancer Biology, 28, 24-30
Open this publication in new window or tab >>Cancer exosomes and NKG2D receptor-ligand interactions: impairing NKG2D-mediated cytotoxicity and anti-tumour immune surveillance
2014 (English)In: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 28, p. 24-30Article, review/survey (Refereed) Published
Abstract [en]

Human cancers constitutively produce and release endosome-derived nanometer-sized vesicles called exosomes that carry biologically active proteins, messenger and micro RNAs and serve as vehicles of intercellular communication. The tumour exosomes are present in the blood, urine and various malignant effusions such as peritoneal and pleural fluid of cancer patients and can modulate immune cells and responses thus deranging the immune system of cancer patients and giving advantage to the cancer to establish and spread itself. Here, the role of exosomes in the NKG2D receptor ligand system's interactions is discussed. The activating NK cell receptor NKG2D and its multiple ligands, the MHC class I-related chain (MIC) A/B and the retinoic acid transcript-1/UL-16 binding proteins (RAET1/ULBP) 1-6 comprise a powerful stress-inducible danger detector system that targets infected, inflamed and malignantly transformed cells and plays a decisive role in anti-tumour immune surveillance. Mounting evidence reveals that the MIC- and RAET1/ULBP ligand family members are enriched in the endosomal compartment of various tumour cells and expressed and released into the intercellular space and bodily fluids on exosomes thus preserving their entire molecule, three-dimensional protein structure and biologic activity. The NKG2D ligand-expressing exosomes serve as decoys with a powerful ability to down regulate the cognate receptor and impair the cytotoxic function of NK-, NKT-, gamma/delta- and cytotoxic T cells. This review summarizes recent findings concerning the role of NKG2D receptor ligand system in cancer with emphasis on regulation of NKG2D ligand expression and the immunosuppressive role of exosomally expressed NKG2D ligands.

Keywords
Exosomes, Cancer, NKG2D, MICA/B, RAET1, ULBP, NK cells, Cytotoxicity, Tumour surveillance, immune suppression
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-95869 (URN)10.1016/j.semcancer.2014.02.010 (DOI)000343019900004 ()
Available from: 2014-12-03 Created: 2014-11-06 Last updated: 2018-06-07Bibliographically approved
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