Intratumoral injection of Propionibacterium acnes suppresses malignant melanoma by enhancing Th1 immune responses.
Intratumoral injection of Propionibacterium acnes suppresses malignant melanoma by enhancing Th1 immune responses.
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肿瘤内注射痤疮丙酸杆菌的注射可通过增强Th1免疫反应来抑制恶性黑色素瘤。
DOI：
10.1371/journal.pone.0029020
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Mizutani H
中科院分区：
文献类型：
--
作者：
Tsuda K;Yamanaka K;Linan W;Miyahara Y;Akeda T;Nakanishi T;Kitagawa H;Kakeda M;Kurokawa I;Shiku H;Gabazza EC;Mizutani H
恶性黑色素瘤(MM)是一种预后较差的侵袭性皮肤恶性肿瘤，已用过许多可能的治疗药物，但大多效果不佳。痤疮丙酸杆菌(P.acnes)是一种耐氧厌氧革兰氏阳性菌，可引起痤疮和炎症。痤疮假单胞菌被吞噬细胞吞噬加工后，通过产生IL-12、干扰素-γ和肿瘤坏死因子-α等细胞因子，诱导产生较强的Th1型细胞因子免疫应答。痤疮假单胞菌诱导的Th1细胞因子可拮抗Th2介导的特异性过敏反应。痤疮假单胞菌诱导的这种炎症反应已被认为具有抗肿瘤活性，但其对多发性骨髓瘤的作用尚未得到充分评价。我们在MM小鼠模型中分析了接种痤疮杆菌疫苗的抗肿瘤活性。瘤内注射痤疮杆菌通过诱导皮肤和全身Th1型细胞因子的表达，包括与皮下肉芽肿形成相关的肿瘤坏死因子-α和干扰素-γ，在体内成功地保护宿主免受黑色素瘤的侵袭。痤疮肺炎杆菌治疗后，肿瘤组织中有肿瘤坏死因子-α和干扰素-γ阳性T细胞。在小鼠的脾中，肿瘤坏死因子α和干扰素γ产生CD8+T细胞增加，有趣的是，单核细胞的数量也增加。这些观察结果表明，接种痤疮巴氏杆菌疫苗可诱导全身和局部抗肿瘤反应。总之，这项研究表明，接种痤疮假单胞菌疫苗可能是MM的一种有效的治疗替代方案。
Malignant melanoma (MM) is an aggressive cutaneous malignancy associated with poor prognosis; many putatively therapeutic agents have been administered, but with mostly unsuccessful results. Propionibacterium acnes (P. acnes) is an aerotolerant anaerobic gram-positive bacteria that causes acne and inflammation. After being engulfed and processed by phagocytes, P. acnes induces a strong Th1-type cytokine immune response by producing cytokines such as IL-12, IFN-γ and TNF-α. The characteristic Th2-mediated allergic response can be counteracted by Th1 cytokines induced by P. acnes injection. This inflammatory response induced by P. acnes has been suggested to have antitumor activity, but its effect on MM has not been fully evaluated. We analyzed the anti-tumor activity of P. acnes vaccination in a mouse model of MM. Intratumoral administration of P. acnes successfully protected the host against melanoma progression in vivo by inducing both cutaneous and systemic Th1 type cytokine expression, including TNF-α and IFN-γ, which are associated with subcutaneous granuloma formation. P. acnes-treated tumor lesions were infiltrated with TNF-α and IFN-γ positive T cells. In the spleen, TNF-α as well as IFN-γ producing CD8+T cells were increased, and interestingly, the number of monocytes was also increased following P. acnes administration. These observations suggest that P. acnes vaccination induces both systemic and local antitumor responses. In conclusion, this study shows that P. acnes vaccination may be a potent therapeutic alternative in MM.
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影响因子：
15.3
作者：
Yoneyama, H;Matsuno, K;Zhang, Y;Murai, M;Itakura, M;Ishikawa, S;Hasegawa, G;Naito, M;Asakura, H;Matsushima, K
通讯作者：
Matsushima, K
影响因子：
6.4
作者：
KELLER, R;KEIST, R;VANDERMEIDE, PH
通讯作者：
VANDERMEIDE, PH
影响因子：
15.9
作者：
Dannull, J;Su, Z;Vieweg, J
通讯作者：
Vieweg, J
DOI：
10.1073/pnas.0601554103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Liu, HY;Komai-Koma, M;Liew, FY
通讯作者：
Liew, FY
影响因子：
4.6
作者：
Sugisaki, Hitomi;Yamanaka, Keiichi;Mizutani, Hitoshi
通讯作者：
Mizutani, Hitoshi