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Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Th17 Cells and IL-17 As Novel Immune Targets in Ovarian Cancer Therapy
Monika Bilska1, Anna Pawłowska2, Ewelina Zakrzewska3
1The First Department of Oncological Gynecology and Gynecology in Independent Public Teaching Hospital No. 1 in Lublin (Poland), Staszica 16, 20-081 Lublin, Poland.
Abstract:
Ovarian cancer (OC) is usually diagnosed at an advanced stage and is related with poor prognosis. Despite numerous studies, the pathogenesis of OC is still unknown. Recent studies indicate the role of the immune system in the development and spread of OC. The identification of factors and mechanisms involved in that process and their modulation is crucial for creating effective antitumor therapy. We investigated the potential role of Th17 cells in OC patients (n = 71) by analyzing the frequencies of Th17 cells in three different environments, i.e., peripheral blood (PB), peritoneal fluid (PF), and tissue (Th17 infiltrating cells), and the concentration of IL-17A in plasma and PF of patients in terms of their clinical and prognostic significance. Th17 cells were analyzed by flow cytometry as a percentage of CD4+ lymphocytes that expressed intracellular expression of IL-17A. The level of IL-17A in plasma and PF were determined by ELISA. Our results showed accumulation of Th17 cells among tumor-infiltrating CD4+ lymphocytes (p < 0.001 in relation to PB). Moreover, the percentage of Th17 cells in both PB and PF of OC patients was significantly lower than that in benign tumors group (n = 35). There were no significant differences in the percentage of Th17 cells in PB, PF, and tissue in relation to clinicopathological characteristics of OC patients and survival. The lower percentage of Th17 cells in the PB and PF of OC patients may promote evasion of host immune response by cancer cells. The concentration of IL-17A in plasma of OC patients was higher (p < 0.0001) than that in both benign tumors and control group (n = 10). The PF IL-17A level in OC patients was higher (p < 0.0001) than that in women with benign ovarian tumors, indicating its synthesis in OC microenvironment. Higher IL-17A level in PF is correlated with longer (median: 36.5 vs. 27 months) survival of OC patients.
Insights
This study found lower frequencies of T helper 17 (Th17) cells in ovarian cancer patients, suggesting immune evasion. However, higher IL-17A levels in peritoneal fluid correlated with improved survival in ovarian cancer.
Area of Science:
- Immunology
- Oncology
- Gynecologic Oncology
Background:
- Ovarian cancer (OC) often presents at advanced stages with poor prognosis.
- The pathogenesis of OC remains largely unknown, with emerging evidence implicating the immune system.
- Understanding immune factors in OC is critical for developing effective antitumor therapies.
Purpose of the Study:
- To investigate the role of T helper 17 (Th17) cells and IL-17A in ovarian cancer.
- To analyze Th17 cell frequencies in peripheral blood, peritoneal fluid, and tumor tissue.
- To assess the clinical and prognostic significance of Th17 cells and IL-17A in OC patients.
Main Methods:
- Flow cytometry was used to quantify Th17 cells (CD4+ lymphocytes expressing intracellular IL-17A).
- Enzyme-linked immunosorbent assay (ELISA) determined IL-17A concentrations in plasma and peritoneal fluid.
- Analysis included 71 OC patients, 35 benign tumor patients, and 10 controls.
Main Results:
- Th17 cells were significantly accumulated in tumor-infiltrating lymphocytes compared to peripheral blood.
- OC patients exhibited lower percentages of Th17 cells in peripheral blood and peritoneal fluid versus benign tumors.
- Plasma IL-17A levels were elevated in OC patients, and peritoneal fluid IL-17A was higher, indicating local synthesis.
- Higher peritoneal fluid IL-17A levels correlated with longer patient survival (median 36.5 vs. 27 months).
Conclusions:
- Reduced Th17 cell frequencies in OC patients may facilitate immune evasion by cancer cells.
- Elevated IL-17A in the OC microenvironment, particularly in peritoneal fluid, is associated with a favorable prognosis.
- Targeting IL-17A pathways could be a potential therapeutic strategy for ovarian cancer.
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