Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian Cancer

Ovarian cancer (OC) is one of the deadliest gynecological cancers. Recent studies suggest a crucial role of inflammatory immune system cells in the progression and metastasis of OC. The understanding of inflammatory mechanisms is pivotal for the selection of a biomarker that allows the differentiati...

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Main Authors: Iwona Wertel, Dorota Suszczyk, Anna Pawłowska, Monika Bilska, Agata Chudzik, Wiktoria Skiba, Roman Paduch, Jan Kotarski
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2020/1715064
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author Iwona Wertel
Dorota Suszczyk
Anna Pawłowska
Monika Bilska
Agata Chudzik
Wiktoria Skiba
Roman Paduch
Jan Kotarski
author_facet Iwona Wertel
Dorota Suszczyk
Anna Pawłowska
Monika Bilska
Agata Chudzik
Wiktoria Skiba
Roman Paduch
Jan Kotarski
author_sort Iwona Wertel
collection DOAJ
description Ovarian cancer (OC) is one of the deadliest gynecological cancers. Recent studies suggest a crucial role of inflammatory immune system cells in the progression and metastasis of OC. The understanding of inflammatory mechanisms is pivotal for the selection of a biomarker that allows the differentiation between malignant and benign tumors, monitoring the progression of the disease, and identification of patients that will respond to implemented treatment. Our study is aimed at evaluating the profile of IL-6 in the plasma and peritoneal fluid (PF) of patients with various clinical manifestations of OC (n=78). We also examined the relationship between IL-6 and PD-L1/PD-L2 positive CD45+CD14+ inflammatory cell (MO/MA) levels in three OC environments (TME): peripheral blood (PB), PF, and tumor (TT) and their clinical and prognostic relevance in OC patients. The expression of PD-L1/PD-L2 molecules was analyzed by flow cytometry. The IL-6 levels were determined by ELISA. We found an elevated level of PD-L1/PD-L2 positive MO/MA in TT compared to PB (p<0.0001). Significantly higher (p<0.0001) levels of IL-6 were observed in PF of the OC patients than in the benign ovarian tumor group (n=31). Additionally, we found higher IL-6 levels in PF than in the plasma of the OC patients. Interestingly, accumulation of IL-6 was observed in PF of patients with low-differentiated OC and correlated with worse prognosis. Moreover, we observed correlations between the level of IL-6 and CD45+CD14+ cells and between CD45+CD14+PD-L1+ cells and the IL-6 level in PF. For the first time, we discovered that the higher percentage of CD45+CD14+PD-L2+ cells in PF predicts better survival of OC patients. Our study suggests that CD45+CD14+PD-L2+ cells and IL-6 may be predictive biomarkers for OC patients. Understanding how the composition of TME changes during OC development and progression is a prerequisite for projecting new therapeutic strategies. Overall, further validation research is warranted.
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spelling doaj-art-9c49a56718c14a598b5e19ec6d80d8612025-08-20T02:18:28ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/17150641715064Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian CancerIwona Wertel0Dorota Suszczyk1Anna Pawłowska2Monika Bilska3Agata Chudzik4Wiktoria Skiba5Roman Paduch6Jan Kotarski7Independent Laboratory of Cancer Diagnostics and Immunology, I Chair and Department of Oncological Gynaecology and Gynaecology, Medical University of Lublin, Staszica 16, Lublin 20-081, PolandIndependent Laboratory of Cancer Diagnostics and Immunology, I Chair and Department of Oncological Gynaecology and Gynaecology, Medical University of Lublin, Staszica 16, Lublin 20-081, PolandIndependent Laboratory of Cancer Diagnostics and Immunology, I Chair and Department of Oncological Gynaecology and Gynaecology, Medical University of Lublin, Staszica 16, Lublin 20-081, PolandIndependent Public Clinical Hospital No. 1, Medical University of Lublin, Staszica 16, Lublin 20-081, PolandIndependent Laboratory of Cancer Diagnostics and Immunology, I Chair and Department of Oncological Gynaecology and Gynaecology, Medical University of Lublin, Staszica 16, Lublin 20-081, PolandStudents’ Scientific Association, Independent Laboratory of Cancer Diagnostics and Immunology, I Chair and Department of Gynecologic Oncology and Gynecology, Medical University of Lublin, Staszica 16, Lublin 20-081, PolandDepartment of Virology and Immunology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, PolandI Chair and Department of Oncological Gynaecology and Gynaecology, Medical University of Lublin, Staszica 16, Lublin 20-081, PolandOvarian cancer (OC) is one of the deadliest gynecological cancers. Recent studies suggest a crucial role of inflammatory immune system cells in the progression and metastasis of OC. The understanding of inflammatory mechanisms is pivotal for the selection of a biomarker that allows the differentiation between malignant and benign tumors, monitoring the progression of the disease, and identification of patients that will respond to implemented treatment. Our study is aimed at evaluating the profile of IL-6 in the plasma and peritoneal fluid (PF) of patients with various clinical manifestations of OC (n=78). We also examined the relationship between IL-6 and PD-L1/PD-L2 positive CD45+CD14+ inflammatory cell (MO/MA) levels in three OC environments (TME): peripheral blood (PB), PF, and tumor (TT) and their clinical and prognostic relevance in OC patients. The expression of PD-L1/PD-L2 molecules was analyzed by flow cytometry. The IL-6 levels were determined by ELISA. We found an elevated level of PD-L1/PD-L2 positive MO/MA in TT compared to PB (p<0.0001). Significantly higher (p<0.0001) levels of IL-6 were observed in PF of the OC patients than in the benign ovarian tumor group (n=31). Additionally, we found higher IL-6 levels in PF than in the plasma of the OC patients. Interestingly, accumulation of IL-6 was observed in PF of patients with low-differentiated OC and correlated with worse prognosis. Moreover, we observed correlations between the level of IL-6 and CD45+CD14+ cells and between CD45+CD14+PD-L1+ cells and the IL-6 level in PF. For the first time, we discovered that the higher percentage of CD45+CD14+PD-L2+ cells in PF predicts better survival of OC patients. Our study suggests that CD45+CD14+PD-L2+ cells and IL-6 may be predictive biomarkers for OC patients. Understanding how the composition of TME changes during OC development and progression is a prerequisite for projecting new therapeutic strategies. Overall, further validation research is warranted.http://dx.doi.org/10.1155/2020/1715064
spellingShingle Iwona Wertel
Dorota Suszczyk
Anna Pawłowska
Monika Bilska
Agata Chudzik
Wiktoria Skiba
Roman Paduch
Jan Kotarski
Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian Cancer
Journal of Immunology Research
title Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian Cancer
title_full Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian Cancer
title_fullStr Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian Cancer
title_full_unstemmed Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian Cancer
title_short Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian Cancer
title_sort prognostic and clinical value of interleukin 6 and cd45 cd14 inflammatory cells with pd l1 pd l2 expression in patients with different manifestation of ovarian cancer
url http://dx.doi.org/10.1155/2020/1715064
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