Commensal gut bacteria help regulate the immune system and can, in that capacity, significantly influence patient responses to cancer immunotherapy. In a March paper in the Journal of Experimental Medicine, a research team led by Ludwig Chicago’s Ralph Weichselbaum and Yang-Xin Fu of the University of Texas Southwestern Medical Center reported that they can aid immunotherapy more directly as well. The researchers found that one denizen of the gut, Bifidobacterium, also preferentially accumulates in tumors, where it can stimulate responses to anti-CD47 immunotherapy (an experimental therapy first developed by Ludwig Stanford’s Irv Weissman and his colleagues). The bacteria, it turns out, work this wonder through dendritic cells, sentinels of the immune system that help activate antitumor immune responses. Ralph, Yang-Xin and colleagues show that their intratumoral presence boosts the signaling of a protein in dendritic cells named STING, which activates immune-stimulating factors known as interferons. Systemic administration of Bifidobacteria to mice led to their preferential accumulation in tumors, where they stimulated responses to subsequent anti-CD47 immunotherapy. Their removal with antibiotics eliminated the effect. The finding could have significant implications for broadening the efficacy of anti-CD47 immunotherapy, which is now being evaluated in clinical trials as a treatment for multiple tumor types.
This article appeared in the August 2020 issue of Ludwig Link. Click here to download a PDF (2 MB).