Melanoma Meets Microbiome

Source: NEJM Journal Watch, December 2015

Two groundbreaking studies implicate specific bacterial species in regulating gut immunity and response to immunotherapy in physically distant tumors — an entirely new angle in cancer therapy.

The influence of the microbiome on cancer susceptibility and therapy effectiveness has been shown. Furthermore, commensal organisms have critical roles in tuning immunity at epithelial surfaces, suggesting their potential role in regulating immunotherapy response.

Sivan and colleagues compared genetically identical mice obtained from two different mouse facilities that had different gut microbiota. Interestingly, these mice reacted differently to syngeneic implanted mouse melanoma tumors, apparently because of differences in the vigor of their anti-tumor T-cell responses. These differences were eliminated by cohousing and could be reversed by fecal transplantation from the mice with anti-tumor immunity, implicating the gut microbiome. Furthermore, fecal transfer augmented responses to anti–PD-L1 immunotherapy. Following sequencing of the bacteria, they found that Bifidobacterium species were overrepresented in mice with better anti-tumor immunity, and introduction of those species into the other mice produced anti-tumor responses.