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IL-10 derived from Hepatocarcinoma cells improves human induced regulatory T cells function via JAK1/STAT5 pathway in tumor microenvironment.
- Source :
-
Molecular immunology [Mol Immunol] 2021 May; Vol. 133, pp. 163-172. Date of Electronic Publication: 2021 Mar 02. - Publication Year :
- 2021
-
Abstract
- Forkhead box P3 (Foxp3) expressing CD4 <superscript>+</superscript> CD25 <superscript>+</superscript> regulatory T cells (Tregs), an essential subset of immune T cells for maintaining immune homeostasis is implicated as a negative regulator in an anti-tumor immune response. Current researches suggest that reducing tumor-infiltrating Tregs contribute to enhanced anti-cancer effect. However, the mechanism of infiltration of a large number of Tregs into tumor tissues is still unclear. In this study, human induced Tregs (iTregs) were co-cultured with human hepatocytes and various types of cancer cells (HepG2, NSCLC, and AsPC-1) supernatants. Foxp3, multiple cytokines, levels of apoptosis and suppressive ability of iTregs were detected by FACS. Western blot was employed to test of proteins. Impact of HepG2 supernatants on T cell subpopulations differentiation, cytokines in supernatants were examed by FACS and ELISA respectively. Anti-IL-10R antibody and JAK1 inhibitor were used to reconfirm the role of tumor-derived IL-10 play in the regulation on iTregs. Hepatocarcinoma cells (HCC) supernatants treatment increases Foxp3 stability and reduces apoptosis level in human iTregs without influencing its differentiation trend. Furthermore, IL-10 was found to be extremely higher in HCC supernatants than other groups, IL-10R blockade neutralize the effect of HCC supernatants on iTregs in vitro obviously. HCC supernatants also reversed IL-1β/6 triggered decline on Foxp3 which may be related to higher expression of JAK1 and elevated phosphorylation level of STAT5 induced by IL-10. Our results suggest that improved stability and abnormal accumulation of Tregs in tumor microenvironment is IL-10/JAK1/STAT5 signal pathway-dependent and provide a novel approach for improving the efficiency of anti-tumor immunotherapy.<br /> (Copyright © 2021. Published by Elsevier Ltd.)
- Subjects :
- Adenocarcinoma pathology
Adenoma pathology
Apoptosis immunology
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor
Coculture Techniques
Culture Media, Conditioned chemistry
Forkhead Transcription Factors analysis
Hep G2 Cells
Hepatocytes metabolism
Humans
Immunotherapy methods
Interleukin-10 analysis
Janus Kinase 1 antagonists & inhibitors
Lung Neoplasms pathology
Pancreatic Neoplasms pathology
Receptors, Interleukin-10 antagonists & inhibitors
Interleukin-10 immunology
Janus Kinase 1 metabolism
Liver Neoplasms pathology
STAT5 Transcription Factor metabolism
T-Lymphocytes, Regulatory immunology
Tumor Microenvironment immunology
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9142
- Volume :
- 133
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33667986
- Full Text :
- https://doi.org/10.1016/j.molimm.2021.02.014