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Science ; 350(6264): 1084-9, 2015 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-26541606

RESUMO

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.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/imunologia , Bifidobacterium/imunologia , Microbioma Gastrointestinal/imunologia , Melanoma/imunologia , Melanoma/terapia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/terapia , Animais , Bifidobacterium/genética , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Transplante de Microbiota Fecal , Regulação da Expressão Gênica , Humanos , Imunidade/genética , Imunoterapia/métodos , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética , Simbiose , Linfócitos T/imunologia , Microambiente Tumoral/imunologia
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