Sivan Ayelet, Corrales Leticia, Hubert Nathaniel, Williams Jason B, Aquino-Michaels Keston, Earley Zachary M, Benyamin Franco W, Lei Yuk Man, Jabri Bana, Alegre Maria-Luisa, Chang Eugene B, Gajewski Thomas F
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Science. 2015 Nov 27;350(6264):1084-9. doi: 10.1126/science.aac4255. Epub 2015 Nov 5.
T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)-specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8(+) T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.
实体瘤中的T细胞浸润与患者的良好预后相关,但个体间免疫反应差异的潜在机制尚不清楚。一种可能的调节因子可能是肠道微生物群。我们比较了携带不同共生微生物群的小鼠体内黑色素瘤的生长情况,并观察到自发抗肿瘤免疫的差异,这种差异在同笼饲养或粪便移植后消失。对16S核糖体RNA进行测序确定双歧杆菌与抗肿瘤作用相关。单独口服双歧杆菌可将肿瘤控制改善至与程序性细胞死亡蛋白1配体1(PD-L1)特异性抗体治疗(检查点阻断)相同的程度,联合治疗几乎完全抑制了肿瘤生长。树突状细胞功能增强,导致肿瘤微环境中CD8(+) T细胞启动和积累增强,介导了这一效应。我们的数据表明,操纵微生物群可能会调节癌症免疫治疗。