Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: Role of IDO
Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: Role of IDO
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DOI：
10.4049/jimmunol.177.4.2391
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发表时间：
2006-08-15
影响因子：
4.4
通讯作者：
Mukherjee, Pinku
中科院分区：
文献类型：
--
作者：
D Basu, Gargi;Tinder, Teresa L.;Mukherjee, Pinku
我们报道，塞来昔布（一种特异性环氧化酶-2 （COX-2）抑制剂）与树突状细胞肿瘤疫苗联合使用可显著增强疫苗在减少原发肿瘤负担、预防转移和提高生存率方面的效力。这种联合治疗在MMTV-PyV NIT小鼠中进行了测试，这些小鼠发生自发性乳腺肿瘤并转移到肺部和骨髓。疫苗效力的提高与肿瘤特异性ctl的增加有关。CTL活性的增强归因于肿瘤相关IDO水平的显著降低，IDO是T细胞活性的负调节因子。我们目前的数据表明，体内抑制COX-2活性可调节肿瘤微环境中的IDO表达；这在MDA-MB-231人乳腺癌细胞系中得到进一步证实。因此，cox -2通过调节IDO诱导免疫抑制的新机制已经出现，这可能对设计未来的癌症疫苗具有指导意义。
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 NIT 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.