Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling
Year: 2020
Type: article
Abstract: Most studies focus on how intestinal microbiota influence cancer immunotherapy through activating gut immunity. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor microenvironment. Using one defined anaerobic gut microbiota to track whether microbiota interact with host immunity, we observed that Bifidobacterium facilitates local anti-CD47 immunotherapy on tumor tissues through the capacity to accumulate within the tumor microenvironment. Systemic administration of Bifidobacterium leads to its accumulation within the tumor and converts the nonresponder mice into responders to anti-CD47 immunotherapy in a stimulator of interferon genes (STING)- and interferon-dependent fashion. Local delivery of Bifidobacterium potently stimulates STING signaling and increases cross-priming of dendritic cells after anti-CD47 treatment. Our study identifies the mechanism by which gut microbiota preferentially colonize in tumor sites and facilitate immunotherapy via STING signaling.
DOI: 10.1084/jem.20192282
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G1024892609, Microbiota and the anti-tumor action of anti-CD47 immunomodulation., Targeting Tumor Tissues Increases DNA Sensing to Bridge Innate and Adaptive Immunity, G2526232395, TNF family members for lymph angiogenesis and lymph node hypertrophy, G7060608162, Recruitment of Established Investigators, Center for Interdisciplinary Study of Inflammatory Intestinal DIsorders (C-IID)
OpenAlex ID: W3009785090