Abstract
BackgroundInterleukin-35 (IL-35) has been reported to play an important role in the progression of cancers. The role of IL-35 in prostate cancer (PCA) is not well understood. In this study, we investigated the effects of IL-35 on PCA and its immunoregulatory effect on PCA.MethodsThe protein and mRNA expression of IL-35 in PCA cells was detected by western blot and RT-PCR. The invasion and migration of cells were detected using transwell and wound‐healing assays. A CCK-8 assay was conducted to observe cell proliferation. In vivo, IL-35 plasma concentration was test by enzyme-linked immunosorbent assay. The role of IL-35 in tumour cell proliferation and angiogenesis of mice was detected by immunohistochemical stains. The mouse survival and tumour volumes were calculated, and lung metastasis rate was detected by HE staining. The modulatory effects of IL-35 on myeloid-derived inhibitory cells (MDSCs), regulatory T cells (Tregs), CD4+ T cells and CD8+ T cells from PCA mice were investigated by immunohistochemical stains and flow cytometry.ResultsHigh levels of IL-35 significantly promoted the migration, invasion and cell proliferation of PCA cells in vitro. IL-35 was associated with tumour growth, metastasis and poor prognosis in PCA mice. Additionally, high levels of IL-35 significantly increased the proportions of MDSCs and Tregs and decreased the proportions of CD4+ and CD8+ T cells in the spleen, blood and tumour microenvironment. The IL-35 neutralizing antibody played the opposite role.ConclusionsIL-35 contributed to the progression of PCA through promoting cell proliferation and tumour angiogenesis. IL-35 might limit the anti-tumour immune response by upregulating the proportions of Tregs and MDSCs and by reducing the proportions of CD4+ and CD8+ T cells. IL-35 might serve as a novel therapeutic target for PCA.
Highlights
Interleukin-35 (IL-35) has been reported to play an important role in the progression of cancers
IL-12 is composed of p35 and p40, and IL-27 is composed of p28 and Epstein Barr virus induced 3 (EBI3)
IL‐35 expression in prostate cancer (PCA) cell lines First, we investigated the expression of IL-35 in four PCA cell lines, at the same time, to screen the appropriate PCA cell lines for the in vitro study
Summary
Interleukin-35 (IL-35) has been reported to play an important role in the progression of cancers. The role of IL-35 in prostate cancer (PCA) is not well understood. Prostate cancer (PCA) is the second most common malignant tumour and the fifth leading cause of cancerassociated mortality in men worldwide [1]. Studies have shown that some tumour cells evade immune recognition and killing by activating the negative stimulus. Zhu et al Cancer Cell Int (2020) 20:487 signal and by regulating the inhibitory immune response [4]. Tumour cells can recruit immunosuppressive cells, such as regulatory T cells (Tregs) and myeloid-derived inhibitory cells (MDSCs), and mediate the release of immunosuppressive factors directly or indirectly. Some cytokines with immunosuppressive functions, such as transforming growth factor (TGF)-β, interleukin (IL)-6, and IL-35, have attracted great attention [5, 6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
