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

Research output: Contribution to journalArticle

100 Citations (Scopus)

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
StatePublished - Aug 15 2006

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Cancer Vaccines
Cyclooxygenase 2 Inhibitors
Celecoxib
Cyclooxygenase 2
Vaccine Potency
Breast Neoplasms
Neoplasm Metastasis
Tumor Microenvironment
Human Mammary Glands
Tumor Burden
Immunosuppression
Dendritic Cells
Neoplasms
Vaccines
Bone Marrow
T-Lymphocytes
Cell Line
Lung
Survival
Therapeutics

ASJC Scopus subject areas

  • 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.

Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine : Role of IDO. / Basu, Gargi D.; Tinder, Teresa L.; Bradley, Judy M.; Tu, Tony; Hattrup, Christine L.; Pockaj, Barbara A; Mukherjee, Pinku.

In: Journal of Immunology, Vol. 177, No. 4, 15.08.2006, p. 2391-2402.

Research output: Contribution to journalArticle

Basu, GD, Tinder, TL, Bradley, JM, Tu, T, Hattrup, CL, Pockaj, BA & Mukherjee, P 2006, 'Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: Role of IDO', Journal of Immunology, vol. 177, no. 4, pp. 2391-2402.
Basu GD, Tinder TL, Bradley JM, Tu T, Hattrup CL, Pockaj BA et al. Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: Role of IDO. Journal of Immunology. 2006 Aug 15;177(4):2391-2402.
Basu, Gargi D. ; Tinder, Teresa L. ; Bradley, Judy M. ; Tu, Tony ; Hattrup, Christine L. ; Pockaj, Barbara A ; Mukherjee, Pinku. / Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine : Role of IDO. In: Journal of Immunology. 2006 ; Vol. 177, No. 4. pp. 2391-2402.
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