Publication: Inhibition of IL-10 and TGF-β receptors on dendritic cells enhances activation of effector T-cells to kill cholangiocarcinoma cells
Issued Date
2018-06-03
Resource Type
ISSN
2164554X
21645515
21645515
Other identifier(s)
2-s2.0-85042237268
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Mahidol University
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SCOPUS
Bibliographic Citation
Human Vaccines and Immunotherapeutics. Vol.14, No.6 (2018), 1423-1431
Suggested Citation
Chutamas Thepmalee, Aussara Panya, Mutita Junking, Thaweesak Chieochansin, Pa thai Yenchitsomanus Inhibition of IL-10 and TGF-β receptors on dendritic cells enhances activation of effector T-cells to kill cholangiocarcinoma cells. Human Vaccines and Immunotherapeutics. Vol.14, No.6 (2018), 1423-1431. doi:10.1080/21645515.2018.1431598 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/46004
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Title
Inhibition of IL-10 and TGF-β receptors on dendritic cells enhances activation of effector T-cells to kill cholangiocarcinoma cells
Abstract
© 2018, © 2018 Siriraj Hospital, Mahidol University. Tumor escapes host immune responses by producing immunosuppressive cytokines, such as IL-10 and TGF-β, secreted into the tumor microenvironment. These cytokines play important roles in the suppression of dendritic cell (DC) function, leading to decreased immune responses of the effector CD4 + and CD8 + T cells. To improve DC functions and enhance cytolytic activity of activated effector T-cells, we suppressed the effect of these cytokines on DCs by using specific neutralizing antibodies that inhibit IL-10 and TGF-β receptors. Monocyte-derived DCs generated in vitro showed up-regulation of MHC (HLA-DR) and co-stimulatory molecules (CD40 and CD86). The IL-10 and TGF-β receptors were expressed and localized on cell membrane of DCs, as shown by Western blot analysis and immunofluorescence staining, whereas the IL-10 and TGF-β ligands were detected in the culture supernatants of DCs and cholangiocarcinoma (CCA) cell line, respectively. Inhibition of the IL-10 and TGF-β receptors on DCs by specific neutralizing antibodies significantly increased level of IFN-γ and enhanced cytolytic activity of the DC-activated effector T-cells against CCA cell line. These results indicate that the IL-10 and TGF-β receptors are the targets for inhibition to increase DC functions and enhance cytolytic activity of the DC-activated effector T-cells against CCA cells. Thus, inhibition of the IL-10 and TGF-β receptors on DCs is crucial in the preparation of DC-activated effector T cells for adoptive T-cell therapy.