Abstract
BackgroundThe role of γδ T cells, innate-like lymphocytes with unrestrained MHC, in various malignancies has recently been extensively studied. However, there is limited research regarding γδ T cells in ovarian cancer (OC) patients.MethodsHere, we investigated the distribution patterns of γδ T cells and their main subsets in peripheral blood and tumor tissues among OC patients, benign ovarian tumor (BOT) patients, and age-matched healthy controls (HC) by flow cytometry, as well as the expression levels of IFN-γ and IL-17A secreted from γδ T cells. Immunohistochemical staining was utilized to detect the numbers of γδ T cells and their main subsets in different types of ovarian tumor tissues. Additionally, we also investigated chemotaxis effects on γδ T cells, as well as their cytotoxic activity and proliferation.ResultsWe found that the percentages of γδ T cells and Vδ1 T cells were significantly higher in OC tissues than BOT tissues and normal (N) ovarian tissues, while there were no obvious differences in peripheral blood. Meanwhile, higher numbers of γδ T cells and Vδ1 T cells were observed in OC tissues, and were positively related to advanced clinicopathological features of OC patients. Further, the levels of IFN-γ secreted by γδ T cells were relatively lower, while IL-17A was expressed at a high level in both the peripheral blood and tissues of OC patients. Chemotaxis assay revealed that supernatants derived from OC tissues possessed a stronger capacity to attract and recruit γδ T cells. However, γδ T cells sorted from OC tissues showed weakened cytotoxic activity against ovarian cancer cells, and γδ T cells cocultured with OC tissue supernatants could effectively inhibit the proliferative activity of naïve CD4+ T cells.ConclusionsThese data suggested that γδ T cells might have critical roles in OC progression and potential utilization in treatment approaches or prognosis prediction.
Highlights
The role of γδ T cells, innate-like lymphocytes with unrestrained MHC, in various malignancies has recently been extensively studied
Distribution characteristics of γδ T cells in peripheral blood of ovarian cancer To identify the distribution characteristics of γδ T cells in PB, we measured the relative percentages of γδ T cells in OC patients, benign ovarian tumor (BOT) patients, and healthy controls (HC) via flow cytometry
We identified that Vδ1 T cells were evident in less significant percentages inOC patients, BOT patients, and HCs (19.12% ± 17.2% vs. 18.8% ± 12.96% vs. 17.3% ± 13.8, P > 0.05; Fig. 1b, d), and comprised less than 20% of all γδ T cells in PB
Summary
The role of γδ T cells, innate-like lymphocytes with unrestrained MHC, in various malignancies has recently been extensively studied. There is limited research regarding γδ T cells in ovarian cancer (OC) patients. The capacity of tumor cells to establish an immunosuppressive microenvironment to evade immune surveillance is the major obstacle in tumor immunotherapy [4, 5]. Immunosuppressive cells and inhibitory factors are important components of the tumor immunosuppressive microenvironment, and include regulatory T cells (Tregs), marrow-derived suppressive cells (MDSCs), tumor-associated macrophages (TAMs), interleukin-10 (IL-10), and transforming growth factor (TGF-β). Tregs are vital immunosuppressive cells that contribute to the suppression of immune responses, mediate immune tolerance, and participate in the tumorigenesis, development and metastasis of cancer. Traditional Tregs including CD4+ Tregs and CD8+ Tregs, both αβT cell types, have been extensively studied [6], much less is known about γδ T cells in tumor immunity [7]
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