Curcumin improves the therapeutic efficacy of Listeria(at)-Mage-b vaccine in correlation with improved T-cell responses in blood of a triple-negative breast cancer model 4T1.
Curcumin improves the therapeutic efficacy of Listeria(at)-Mage-b vaccine in correlation with improved T-cell responses in blood of a triple-negative breast cancer model 4T1.
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DOI：
10.1002/cam4.94
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发表时间：
2013-08
期刊：
影响因子：
4
通讯作者：
Gravekamp, Claudia
中科院分区：
文献类型：
--
作者：
Singh, Manisha;Ramos, Ilyssa;Asafu-Adjei, Denise;Quispe-Tintaya, Wilber;Chandra, Dinesh;Jahangir, Arthee;Zang, Xingxing;Aggarwal, Bharat B.;Gravekamp, Claudia
癌症疫苗接种的成功受到肿瘤微环境（TME）中免疫抑制的严重阻碍。白细胞介素（IL）-6是三阴性乳腺癌（TNBC）细胞特别且高度产生的，并且已被认为是TME中免疫抑制的重要贡献者。因此，我们假设IL-6减少可以通过改善T细胞应答来改善针对TNBC癌症的疫苗接种的功效。为了证明这一假设，我们研究了姜黄素（IL-6产生的抑制剂）对在TNBC模型4 T1中接种高度减毒的单核细胞增生李斯特菌（Listeriaat）（编码肿瘤相关抗原（TAA）Mage-b）的影响。测试了使用李斯特菌-Mage-B和姜黄素的两种治疗性疫苗接种策略。第一种免疫策略涉及肿瘤发展后的所有李斯特菌-Mage-B疫苗接种和姜黄素。由于姜黄素已在全世界被消耗，第二种免疫策略涉及肿瘤发生前的姜黄素和肿瘤发生后的李斯特菌-Mage-B的所有治疗性疫苗接种。在此，我们证明姜黄素显著改善了李斯特菌-Mage-B与两种免疫策略的治疗功效，特别是针对TNBC模型（4 T1）中的转移。与肿瘤发生后相比，在肿瘤发生前给予姜黄素时，联合治疗对转移的有效性略高，但显着。在联合治疗中，在肿瘤发展之前使用姜黄素，髓源性抑制细胞（MDSC）的IL-6产生显著降低，IL-12增加，与血液中CD 4和CD 8 T细胞应答的改善相关。我们的研究表明，姜黄素通过逆转肿瘤诱导的免疫抑制来提高李斯特菌-Mage-B疫苗针对TNBC模型4 T1中的转移的功效。这项研究的重点是通过减少免疫抑制来改善癌症疫苗接种。在这里，我们证明姜黄素通过将骨髓来源的抑制细胞转化为免疫刺激表型，即通过减少IL-6和增加IL-12的产生，与改善的T细胞应答和显著减少转移瘤数量相关，从而提高李斯特菌-Mage-B的疫苗效力。本研究的新结果可能为姜黄素改善其他癌症疫苗提供平台。
Success of cancer vaccination is strongly hampered by immune suppression in the tumor microenvironment (TME). Interleukin (IL)-6 is particularly and highly produced by triple-negative breast cancer (TNBC) cells, and has been considered as an important contributor to immune suppression in the TME. Therefore, we hypothesized that IL-6 reduction may improve efficacy of vaccination against TNBC cancer through improved T-cell responses. To prove this hypothesis, we investigated the effect of curcumin, an inhibitor of IL-6 production, on vaccination of a highly attenuated Listeria monocytogenes (Listeriaat), encoding tumor-associated antigens (TAA) Mage-b in a TNBC model 4T1. Two therapeutic vaccination strategies with Listeriaat-Mage-b and curcumin were tested. The first immunization strategy involved all Listeriaat-Mage-b vaccinations and curcumin after tumor development. As curcumin has been consumed all over the world, the second immunization strategy involved curcumin before and all therapeutic vaccinations with Listeriaat-Mage-b after tumor development. Here, we demonstrate that curcumin significantly improves therapeutic efficacy of Listeriaat-Mage-b with both immunization strategies particularly against metastases in a TNBC model (4T1). The combination therapy was slightly but significantly more effective against the metastases when curcumin was administered before compared to after tumor development. With curcumin before tumor development in the combination therapy, the production of IL-6 was significantly decreased and IL-12 increased by myeloid-derived suppressor cells (MDSC), in correlation with improved CD4 and CD8 T-cell responses in blood. Our study suggests that curcumin improves the efficacy of Listeriaat-Mage-b vaccine against metastases in TNBC model 4T1 through reversal of tumor-induced immune suppression. This study is focused on improving cancer vaccination by reducing immune suppression. Here we demonstrate that curcumin improves vaccine efficacy of Listeria-Mage-b by converting myeloid-derived suppressor cells into an immune stimulating phenotype, that is, through reducing IL-6 and increasing IL-12 production, in correlation with improved T cell responses and a dramatic reduction in the number of metastases. The novel results of this study may be a platform for improvement of other cancer vaccines by curcumin.
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DOI：
10.1186/bcr1680
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Berishaj M;Gao SP;Ahmed S;Leslie K;Al-Ahmadie H;Gerald WL;Bornmann W;Bromberg JF
通讯作者：
Bromberg JF
影响因子：
6.4
作者：
Chakravarti, Nitin;Myers, Jeffrey N.;Aggarwal, Bharat B.
通讯作者：
Aggarwal, Bharat B.
影响因子：
4.3
作者：
Deng, Xin-Sheng;Wang, Shuiliang;Thor, Ann D.
通讯作者：
Thor, Ann D.
影响因子：
50.5
作者：
Curigliano, G.;Viale, G.;Goldhirsch, A.
通讯作者：
Goldhirsch, A.
影响因子：
4.8
作者：
Bhattacharyya, Sankar;Mandal, Debaprasad;Sa, Gaurisankar
通讯作者：
Sa, Gaurisankar