The Immune Tolerance of Cancer is Mediated by IDO That is Inhibited by COX-2 Inhibitors Through Regulatory T Cells
- Authors
- Lee, Sung Yong; Choi, Hye Kyoung; Lee, Kyoung Ju; Jung, Jin Yong; Hur, Gyu Young; Jung, Ki Hwan; Kim, Je Hyeong; Shin, Chol; Shim, Jae Jeong; In, Kwang Ho; Kang, Kyung Ho; Yoo, Se Hwa
- Issue Date
- Jan-2009
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Keywords
- COX-2; PGE(2); immune tolerance; IDO; regulatory T cell; Foxp3
- Citation
- JOURNAL OF IMMUNOTHERAPY, v.32, no.1, pp 22 - 28
- Pages
- 7
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF IMMUNOTHERAPY
- Volume
- 32
- Number
- 1
- Start Page
- 22
- End Page
- 28
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/16310
- DOI
- 10.1097/CJI.0b013e31818ac2f7
- ISSN
- 1524-9557
1537-4513
- Abstract
- Prostaglandin (PGE(2)), synthesized by cyclooxygenase-2 (COX-2), is associated with cellular immune tolerance during the process of cancer development. Induction of tolerance requires a specific environment in which dendritic cells and regulatory T cells (T-regs) play an essential role. It was recently shown that maturation of dendritic cells in the presence of indoleamine 2, 3-dioxygenase (IDO) results ill activation of T-regs and inhibition of COX-2 activity regulated IDO expression within the tumor microenvironment. Thus, we hypothesized that the tumor immune tolerance would be inhibited by COX-2 inhibitor and this inhibition would be mediated by IDO-dependent T-regs inhibition. The PGE(2) in Lewis lung cancer cells (3LL) and serum of mice were measured for the evaluation of COX-2 inhibitors' local and systemic effects. The production of PGE(2) in 3LL cells and serum of 3LL tumor-bearing mice were decreased by COX-2 inhibition. However. there were no significant differences in serum PGE2 levels among normal control and celecoxib-treated nontumor-bearing mice. The accumulation of T-regs was reduced in the celecoxib-treated 3LL tumor-bearing mice. In addition, the expressions of COX-2, IDO, and Foxp3 were reduced in the mice treated with a COX-2 inhibitor, and this was found to correlate with a reduction in the size of tumor mass and metastasis. These results suggest that the antitumor effects of COX-2 inhibitors seemed to be correlated with the inhibition of IDO and T-regs. Therefore, COX-2 inhibitors might provide a therapeutic strategy for T-regs-induced tumor immune tolerance.
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- Appears in
Collections - 2. Clinical Science > Department of Pulmonary, Allergy, and Critical Care Medicine > 1. Journal Articles
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