Ovarian Cancer Research Center, and.
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
JCI Insight. 2018 Feb 22;3(4). doi: 10.1172/jci.insight.94952.
Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here, we report that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer. Depletion of bacteria with vancomycin decreased the rate of tumor growth in mice from The Jackson Laboratory receiving ACT, whereas treatment with neomycin and metronidazole had no effect, indicating the role of specific bacteria in host response. Vancomycin treatment induced an increase in systemic CD8α+ DCs, which sustained systemic adoptively transferred antitumor T cells in an IL-12-dependent manner. In subjects undergoing allogeneic hematopoietic cell transplantation, we found that oral vancomycin also increased IL-12 levels. Collectively, our findings demonstrate an important role played by the gut microbiota in the antitumor effectiveness of ACT and suggest potentially new avenues to improve response to ACT by altering the gut microbiota.
过继性 T 细胞疗法（ACT）是一种有前途的恶性肿瘤治疗新方法。在这里，我们报告称，在荷瘤小鼠中，过继性 T 细胞的疗效受到肠道微生物组固有组成差异、抗生素治疗或异源粪便转移的显著影响。万古霉素耗尽细菌可降低接受 ACT 的杰克逊实验室小鼠的肿瘤生长速度，而新霉素和甲硝唑治疗则没有影响，这表明特定细菌在宿主反应中起作用。万古霉素治疗诱导全身 CD8α+DC 增加，以 IL-12 依赖的方式维持系统过继转移的抗肿瘤 T 细胞。在接受异基因造血细胞移植的患者中，我们发现口服万古霉素也能增加 IL-12 水平。总的来说，我们的研究结果表明肠道微生物群在 ACT 的抗肿瘤疗效中起着重要作用，并提示通过改变肠道微生物群来提高对 ACT 反应的潜在新途径。
