Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Eur J Immunol. 2011 Jan;41(1):246-51. doi: 10.1002/eji.201040773. Epub 2010 Dec 9.
Intravesical inoculation of Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been used for the treatment of bladder cancer. Recent studies implied the requirement of neutrophil infiltration for the antitumor effect. In this study, we found that IL-17 was produced in the bladder after BCG treatment, preceding the infiltration of neutrophils. Neutrophils in the bladder after BCG treatment were reduced in IL-17-deficient mice, in which BCG-induced antitumor effect against intravesically inoculated bladder cancer was abolished. Notably, the level of IL-17 production and the number of neutrophils in BCG-treated bladder was reduced in γδ T-cell-deficient mice but not in CD4-depleted mice. Survival of bladder cancer-inoculated γδ T-cell-deficient mice was not improved by BCG treatment. These results suggest that IL-17-producing γδ T cells play a key role in the BCG-induced recruitment of neutrophils to the bladder, which is essential for the antitumor activity against bladder cancer.
卡介苗(BCG)膀胱内接种已被用于膀胱癌的治疗。最近的研究表明,中性粒细胞浸润是抗肿瘤效应所必需的。在这项研究中,我们发现,BCG 治疗后膀胱内会产生白细胞介素-17(IL-17),先于中性粒细胞浸润。IL-17 缺陷小鼠膀胱内的中性粒细胞减少,其中 BCG 诱导的对膀胱内接种的膀胱癌的抗肿瘤作用被消除。值得注意的是,BCG 处理后膀胱中 IL-17 的产生水平和中性粒细胞数量在 γδ T 细胞缺陷小鼠中减少,但在 CD4 耗竭小鼠中没有减少。BCG 治疗并没有改善膀胱癌接种的 γδ T 细胞缺陷小鼠的生存。这些结果表明,产生白细胞介素-17 的 γδ T 细胞在 BCG 诱导的中性粒细胞募集到膀胱中发挥关键作用,这对于针对膀胱癌的抗肿瘤活性是必不可少的。