Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: Role of IDO

Gargi D. Basu, Teresa L. Tinder, Judy M. Bradley, Tony Tu, Christine L. Hattrup, Barbara A. Pockaj, Pinku Mukherjee

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Abstract

We report that administration of celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, in combination with a dendritic cell-based cancer vaccine significantly augments vaccine efficacy in reducing primary tumor burden, preventing metastasis, and increasing survival. This combination treatment was tested in MMTV-PyV MT mice that develop spontaneous mammary gland tumors with metastasis to the lungs and bone marrow. Improved vaccine potency was associated with an increase in tumor-specific CTLs. Enhanced CTL activity was attributed to a significant decrease in levels of tumor-associated IDO, a negative regulator of T cell activity. We present data suggesting that inhibiting COX-2 activity in vivo regulates IDO expression within the tumor microenvironment; this is further corroborated in the MDA-MB-231 human breast cancer cell line. Thus, a novel mechanism of COX-2-induced immunosuppression via regulation of IDO has emerged that may have implications in designing future cancer vaccines.

Original languageEnglish (US)
Pages (from-to)2391-2402
Number of pages12
JournalJournal of Immunology
Volume177
Issue number4
DOIs
StatePublished - Aug 15 2006

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Basu, G. D., Tinder, T. L., Bradley, J. M., Tu, T., Hattrup, C. L., Pockaj, B. A., & Mukherjee, P. (2006). Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: Role of IDO. Journal of Immunology, 177(4), 2391-2402. https://doi.org/10.4049/jimmunol.177.4.2391