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Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary
Umeå University, Faculty of Medicine, Department of Clinical Sciences.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
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2019 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 29, p. A138-A138Article in journal, Meeting abstract (Other academic) Published
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.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019. Vol. 29, p. A138-A138
National Category
Cancer and Oncology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:umu:diva-170021DOI: 10.1136/ijgc-2019-ESGO.191ISI: 000523502500191OAI: oai:DiVA.org:umu-170021DiVA, id: diva2:1428241
Note

Supplement: 4

Meeting Abstract: P129

Available from: 2020-05-05 Created: 2020-05-05 Last updated: 2020-05-05Bibliographically approved

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Israelsson, PernillaLabani-Motlagh, AlirezaNagaev, IvanDehlin, EvaNagaeva, OlgaLundin, EvaOttander, UlrikaMincheva-Nilsson, Lucia

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Israelsson, PernillaLabani-Motlagh, AlirezaNagaev, IvanDehlin, EvaNagaeva, OlgaLundin, EvaOttander, UlrikaMincheva-Nilsson, Lucia
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Department of Clinical SciencesClinical ImmunologyDepartment of Clinical MicrobiologyClinical BacteriologyDepartment of Medical Biosciences
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International Journal of Gynecological Cancer
Cancer and OncologyObstetrics, Gynecology and Reproductive Medicine

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