c-Src Suppresses Dendritic Cell Antitumor Activity via T Cell Ig and Mucin Protein-3 Receptor.
IR@IMTECH: CSIR-Institute of Microbial Technology, Chandigarh
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| Title |
c-Src Suppresses Dendritic Cell Antitumor Activity via T Cell Ig and Mucin Protein-3 Receptor.
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| Creator |
Gujar, Ravindra
Maurya, Neeraj Yadav, Vinod Gupta, Mamta Arora, Saurabh Khatri, Neeraj Sen, Pradip |
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| Subject |
QR180 Immunology
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| Description |
The enhanced expression of T cell Ig and mucin protein-3 (TIM-3) on tumor-associated dendritic cells (DCs) attenuates antitumor effects of DNA vaccines. To identify a potential target (or targets) for reducing TIM-3 expression on tumor-associated DCs, we explored the molecular mechanisms regulating TIM-3 expression. In this study, we have identified a novel signaling pathway (c-Src→Bruton's tyrosine kinase→transcription factors Ets1, Ets2, USF1, and USF2) necessary for TIM-3 upregulation on DCs. Both IL-10 and TGF-β, which are produced in the tumor microenvironment, upregulated TIM-3 expression on DCs via this pathway. Suppressed expression of c-Src or downstream Bruton's tyrosine kinase, Ets1, Ets2, USF1, or USF2 blocked IL-10- and TGF-β-induced TIM-3 upregulation on DCs. Notably, in vivo knockdown of c-Src in mice reduced TIM-3 expression on tumor-associated DCs. Furthermore, adoptive transfer of c-Src-silenced DCs in mouse tumors enhanced the in vivo antitumor effects of immunostimulatory CpG DNA; however, TIM-3 overexpression in c-Src-silenced DCs blocked this effect. Collectively, our data reveal the molecular mechanism regulating TIM-3 expression in DCs and identify c-Src as a target for improving the efficacy of nucleic acid-mediated anticancer therapy.
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| Publisher |
American Association of Immunologists
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| Date |
2016-09-01
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://crdd.osdd.net/open/1868/1/27.pdf
Gujar, Ravindra and Maurya, Neeraj and Yadav, Vinod and Gupta, Mamta and Arora, Saurabh and Khatri, Neeraj and Sen, Pradip (2016) c-Src Suppresses Dendritic Cell Antitumor Activity via T Cell Ig and Mucin Protein-3 Receptor. Journal of immunology (Baltimore, Md. : 1950), 197 (5). pp. 1650-62. ISSN 1550-6606 |
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| Relation |
http://www.jimmunol.org/content/197/5/1650.long
http://crdd.osdd.net/open/1868/ |
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