Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy.
Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy.
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DOI：
10.1126/science.aac4255
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发表时间：
2015-11-27
期刊：
影响因子：
--
通讯作者：
Gajewski TF
中科院分区：
文献类型：
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作者：
Sivan A;Corrales L;Hubert N;Williams JB;Aquino-Michaels K;Earley ZM;Benyamin FW;Lei YM;Jabri B;Alegre ML;Chang EB;Gajewski TF
实体瘤的T细胞浸润与良好的患者结局相关，但个体之间可变免疫应答的机制尚未得到很好的理解。一种可能的调节剂可能是肠道微生物群。我们比较了黑色素瘤生长在小鼠窝藏不同的肠道微生物群，并观察到自发抗肿瘤免疫的差异，这是消除后，共住房或粪便转移。16 S核糖体RNA测序鉴定双歧杆菌与抗肿瘤作用相关。双歧杆菌单独口服给药改善肿瘤控制的程度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，联合治疗几乎消除了肿瘤生长。增强的树突状细胞功能导致增强的CD 8 + T细胞引发和在肿瘤微环境中的积累介导了该效应。我们的数据表明，操纵微生物群可以调节癌症免疫治疗。
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.