Xu Chengming, Ruan Banjun, Jiang Yinghao, Xue Ting, Wang Zhenyu, Lu Huanyu, Wei Ming, Wang Shan, Ye Zicheng, Zhai Dongsheng, Wang Li, Lu Zifan
State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an 710032, PR China.
Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Fourth Military Medical University, Xi'an 710032, PR China.
Biochem Biophys Res Commun. 2017 Jun 24;488(2):418-424. doi: 10.1016/j.bbrc.2017.05.071. Epub 2017 May 12.
Gut microbiota is critical for maintaining body immune homeostasis and thus affects tumor growth and therapeutic efficiency. Here, we investigated the link between microbiota and tumorgenesis in a mice model of subcutaneous melanoma cell transplantation, and explored the underlying mechanism. We found disruption of gut microbiota by pretreating mice with antibiotics promote tumor growth and remodeling the immune compartment within the primary tumor. Indeed, gut microbial dysbiosis reduced the infiltrated mature antigen-presenting cells of tumor, together with lower levels of co-stimulators, such as CD80, CD86 and MHCII, as well as defective Th1 cytokines, including IFNγ, TNFα, IL12p40, and IL12p35. Meantime, splenic APCs displayed blunted ability in triggering T cell proliferation and IFNγ secretion. However, oral administration of LPS restored the immune surveillance effects and thus inhibited tumor growth in the antibiotics induced gut microbiota dysbiosis group. Taken together, these data highly supported that antibiotics induced gut microbiota dysbiosis promotes tumor initiation, while LPS supplementation would restore the effective immune surveillance and repress tumor initiation.
肠道微生物群对于维持机体免疫稳态至关重要，因此会影响肿瘤生长和治疗效果。在此，我们在皮下黑色素瘤细胞移植小鼠模型中研究了微生物群与肿瘤发生之间的联系，并探究了其潜在机制。我们发现，用抗生素预处理小鼠会破坏肠道微生物群，促进肿瘤生长并重塑原发肿瘤内的免疫微环境。事实上，肠道微生物失调会减少肿瘤中浸润的成熟抗原呈递细胞，同时降低共刺激分子如CD80、CD86和MHCII的水平，以及包括IFNγ、TNFα、IL12p40和IL12p35在内的Th1细胞因子的水平。与此同时，脾脏抗原呈递细胞在触发T细胞增殖和IFNγ分泌方面的能力减弱。然而，口服脂多糖可恢复免疫监视作用，从而抑制抗生素诱导的肠道微生物群失调组中的肿瘤生长。综上所述，这些数据有力地支持了抗生素诱导的肠道微生物群失调促进肿瘤发生，而补充脂多糖可恢复有效的免疫监视并抑制肿瘤发生。
