Gut Microbiota Effects of Vancomycin May Enhance Impact of Radiotherapy Against Cancer

Mouse models suggest that giving patients with cancer a dose of vancomycin before radiation may prepare the immune system to attack tumor cells more effectively.

Gut microbiota can mediate the pathophysiology of many diseases, including cancer, making manipulation of the gut microbiota an emerging area of concern for researchers.

A new study in mouse models conducted by experts from the University of Pennsylvania’s Abramson Cancer Center, published in The Journal of Clinical Investigation, suggests that giving patients with cancer a dose of the antibiotic vancomycin before radiation may prepare the immune system to attack tumor cells more effectively.

Investigators found that oral vancomycin treatment enhances the antitumor effects of hypofractionated radiotherapy in lung/cervical and preclinical melanoma models.

Results were gathered through comparison of vancomycin to a neomycin/metronidazole regimen, administered orally to C57/BL6 mice.

The mice were injected with B-16 Ova or tissue culture 1 tumor cells the following day. When tumors were approximately 50 millimeters—typically within 10 or 11 days—radiotherapy was delivered using an XRAD320iX irradiator.

Investigators observed that the addition of vancomycin prior to radiotherapy produced antitumor effects greater than those of either vancomycin or radiotherapy alone (probability [P] < 0.001, P < 0.001, P = 0.0018 for untreated, vancomycin, and radiotherapy, respectively).

The investigators also found that there were abscopal effects of vancomycin administration, with vancomycin aiding the immune system against tumors away from the treatment area.

Administration of neomycin/metronidazole, on the other hand, did not appear to enhance the antitumor effects of radiotherapy.

Neomycin/metronidazole were chosen in part because they primarily target gram-negative bacteria, in contrast to vancomycin primarily targeting gram-positive bacteria.

Vancomycin is also retained locally in the gut when administered orally, which allowed investigators to conclude that the observations in the study are more likely related to interactions between the gut microbiota and the immune system, rather than a systemic circulation of vancomycin.

It appeared that the vancomycin treatment’s effects on the gut microbiome aided antitumor effects of radiotherapy by improving the function of dendritic cells, messenger cells that the immune system’s T cells depend on.

The study results suggest potential value in future human clinical trials, and pairing vancomycin with radiotherapy may someday be seen as a key part of the armamentarium available for treatment of certain cancers.