Back to Search
Start Over
Interleukin-35 has a tumor-promoting role in hepatocellular carcinoma.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 2021 Feb; Vol. 203 (2), pp. 219-229. Date of Electronic Publication: 2020 Oct 26. - Publication Year :
- 2021
-
Abstract
- Hepatic inflammatory response is a risk factor for liver cancer initiation and progression. Interleukin (IL)-35 is the newest member of the IL-12 cytokine family, and has been reported to play an essential role in the immunosuppressive liver microenvironment. Herein we focus on the expression profiles of IL-35 in hepatocellular carcinoma (HCC) and effects on local immune status. HCC transcriptome array data were downloaded from Gene Expression Omnibus (GEO). Analysis was performed by BRB-Array Tools and Ingenuity Pathway Analysis (IPA) software. Serum IL-35 level was detected by AimPlet bead-based immunoassay. In-situ IL-35 detection was performed by immunohistochemical staining and Western blot. The n-vitro effect of IL-35 on CD4 <superscript>+</superscript> or CD8 <superscript>+</superscript> T cell function was detected by flow cytometry. Our results showed that there were large amounts of IL-35 expressed in HCC serum and tumor tissues. IL-35 expression affects the transcript of thousands of genes, most differentially expressed genes (DEGs), in tumor tissues correlated with T cell immunity. The IL-35 high-expression group exhibited enhancement of regulatory T cells (T <subscript>regs</subscript> ) and impairment of cytolytic T cells. In-vitro experiments proved that exogenous IL-35 stimulated the expression of programmed cell death 1 (PD-1) and lymphocyte activation gene-3 (LAG3) in CD4 <superscript>+</superscript> and CD8 <superscript>+</superscript> T cells. In addition, the stimulating effect was time-dependent. Furthermore, IL-35 inhibited interferon (IFN)-γ secretion by CD4 <superscript>+</superscript> and CD8 <superscript>+</superscript> T cells. Elevated IL-35 had an immune suppressive role in HCC tumor microenvironments through affecting inhibitor receptor expression and cytokine secretion of CD4 <superscript>+</superscript> and CD8 <superscript>+</superscript> T cells. Dissection of the precise targets and underlying molecular mechanisms would mean alternative treatments for HCC patients.<br /> (© 2020 British Society for Immunology.)
- Subjects :
- Animals
CD4-Positive T-Lymphocytes metabolism
CD4-Positive T-Lymphocytes pathology
CD8-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes pathology
Carcinoma, Hepatocellular pathology
Cell Line, Tumor
Cells, Cultured
Humans
Interferon-gamma metabolism
Liver metabolism
Liver pathology
Liver Neoplasms pathology
Mice
Mice, Inbred C57BL
Programmed Cell Death 1 Receptor metabolism
T-Lymphocytes, Regulatory metabolism
Tumor Microenvironment physiology
Carcinogens metabolism
Carcinoma, Hepatocellular metabolism
Interleukins metabolism
Liver Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2249
- Volume :
- 203
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33030251
- Full Text :
- https://doi.org/10.1111/cei.13535