The Microbiome and Melanoma

In This Issue

Our subject is the human microbiome — the microbes and their collective genomes that inhabit our bodies. In our lead story, Jennifer A. Wargo, MD, and colleagues present the latest research on the gut microbiome, the role it plays in patients’ response to immunotherapy and the investigations underway to modify it as a potential tool for melanoma treatment and prevention.

In a companion Q&A, Richard Gallo, MD, PhD, discusses his lab’s exciting early work on the skin microbiome. Dr. Gallo tells the story of how his team discovered a novel strain of skin bacteria that appears to selectively kill melanoma and other cancer cells without harming healthy cells. Dr. Gallo envisions the possibility of one day colonizing such bacteria on human skin and thereby modifying the skin microbiome as a melanoma preventive.

• The Gut Microbiome and Checkpoint Blockade Therapy for Melanoma
• Neoadjuvant Therapy for Melanoma
• A Fascinating (and Unexpected) Discovery: A Potential Cancer Fighter in the Skin Microbiome

From the Editors

Trillions of microorganisms, with a combined weight between two and six pounds, inhabit each human body. They outnumber human cells by a factor of 10. This is the human microbiome.

As early as the fourth century, Chinese medicine appreciated the healing potential of ingesting stool (“yellow soup”) as a treatment for diarrhea. However, it would take centuries for Western medicine to identify bacteria and their role in health, and even longer to acknowledge that some bacteria offer distinct benefits.

From the time that Antonie van Leeuwenhoek first identified bacteria in the 1600s, they were conceived of as harmful invaders, and two centuries later, Robert Koch reinforced this idea when he linked microorganisms to human disease. But the concept that some bacteria could be beneficial began emerging in 1958 when Eiseman and colleagues showed the benefits of fecal enemas in treating Clostridium difficile infection and pseudomembranous colitis. This marked the introduction of fecal microbiota transplants (FMT) into mainstream medicine.¹ Interest in harnessing the microbiome gathered speed after van Nood et al. published a randomized, controlled trial in The New England Journal of Medicine in 2013, confirming Eiseman et al.’s findings.² Ever since, appreciation of the entire microbiome’s impact on health, disease and therapy has continually grown more intense and sophisticated.

In this issue of The Melanoma Letter, we bring you a pair of reports on two different realms of the human microbiome that may have a significant impact on melanoma treatment and prevention — the gut and the skin. Our lead story, by Drs. Thakur, McQuade and Wargo at the University of Texas MD Anderson Cancer Center, explores what we know to date about the gut microbiome’s potential benefits in melanoma, especially in enhancing response to checkpoint blockade therapy. The authors touch on what key factors in this microbiome may affect treatment and how to modify those factors to enhance response. While FMT has already proven an effective microbiome modifier for conditions like inflammatory bowel disease, it has also produced very promising early data in melanoma. And now, investigators are also intensively studying how medications, diet and other lifestyle elements can modify the gut microbiome to boost therapy response.

In our companion piece, a Q&A interview with Richard Gallo, MD, PhD, of the University of California, San Diego, Dr. Gallo tells us the fascinating story of how he and his team almost inadvertently discovered that a strain of common bacteria on the skin (Staphylococcus epidermidis) produces a chemical that can kill melanoma and several other types of cancer cells, while sparing healthy cells. It turns out that about one in five humans have this strain on their skin. Dr. Gallo describes what strategies might be employed to harness it as a treatment — and how it might one day be incorporated in a topical preventive application that would literally alter patients’ skin microbiome, making it more resistant to melanoma.

These stories make it abundantly clear that a long unappreciated symbiotic relationship exists between human health and certain bacteria, and that one day we might well be able to manipulate our microbiome to treat and even prevent melanoma and other diseases.

References

1. Eiseman B, Silen W, Bascom G, Kauvar A. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 1958; 44(5):854–859.
2. Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. NEJM 2013; 368(5):407-15.

Allan C. Halpern, MD • Editor-in-Chief

Ashfaq A. Marghoob, MD • Associate Editor