TY - JOUR
T1 - Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine
T2 - Role of IDO
AU - Basu, Gargi D.
AU - Tinder, Teresa L.
AU - Bradley, Judy M.
AU - Tu, Tony
AU - Hattrup, Christine L.
AU - Pockaj, Barbara A.
AU - Mukherjee, Pinku
PY - 2006/8/15
Y1 - 2006/8/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.177.4.2391
DO - 10.4049/jimmunol.177.4.2391
M3 - Article
C2 - 16888001
AN - SCOPUS:33746906695
SN - 0022-1767
VL - 177
SP - 2391
EP - 2402
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -