Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy

被引:2830
作者
Sivan, Ayelet [1 ]
Corrales, Leticia [1 ]
Hubert, Nathaniel [2 ]
Williams, Jason B. [1 ]
Aquino-Michaels, Keston [3 ]
Earley, Zachary M. [2 ]
Benyamin, Franco W. [1 ]
Lei, Yuk Man [2 ]
Jabri, Bana [2 ]
Alegre, Maria-Luisa [2 ]
Chang, Eugene B. [2 ]
Gajewski, Thomas F. [1 ,2 ]
机构
[1] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Med, Chicago, IL 60637 USA
[3] Univ Chicago, Med Genet Sect, Chicago, IL 60637 USA
关键词
PRESENTING CELL-FUNCTION; DENDRITIC CELLS; T-CELLS; RESPONSES; MICROBIOTA; CANCER; METABOLITES; MATURATION; MELANOMA; SYSTEM;
D O I
10.1126/science.aac4255
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1084 / 1089
页数:7
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